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1. Travis WD, Garg K, Franklin WA, Wistuba II, Sabloff B, Noguchi M, Kakinuma R, Zakowski M, Ginsberg M, Padera R, Jacobson F, Johnson BE, Hirsch F, Brambilla E, Flieder DB, Geisinger KR, Thunnissen F, Kerr K, Yankelevitz D, Franks TJ, Galvin JR, Henderson DW, Nicholson AG, Hasleton PS, Roggli V, Tsao MS, Cappuzzo F, Vazquez M: Bronchioloalveolar carcinoma and lung adenocarcinoma: the clinical importance and research relevance of the 2004 World Health Organization pathologic criteria. J Thorac Oncol; 2006 Nov;1(9 Suppl):S13-9
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  • [Title] Bronchioloalveolar carcinoma and lung adenocarcinoma: the clinical importance and research relevance of the 2004 World Health Organization pathologic criteria.
  • INTRODUCTION: Advances in the pathology and computed tomography (CT) of lung adenocarcinoma and bronchioloalveolar carcinoma (BAC) have demonstrated important new prognostic features that have led to changes in classification and diagnostic criteria.
  • METHODS: The literature and a set of cases were reviewed by a pathology/CT review panel of pathologists and radiologists who met during a November 2004 International Association for the Study of Lung Cancer/American Society of Clinical Oncology consensus workshop in New York.
  • The group addressed the question of whether sufficient data exist to modify the 2004 World Health Organization (WHO) classification of adenocarcinoma and BAC to define a "minimally invasive" adenocarcinoma with BAC.
  • The problems of diffuse and/or multicentric BAC and adenocarcinoma were evaluated.
  • Most lung adenocarcinomas, including those with a BAC component, are invasive and consist of a mixture of histologic patterns.
  • Therefore, they are best classified as adenocarcinoma, mixed subtype.
  • The percentage of BAC versus invasive components in lung adenocarcinomas seems to be prognostically important.
  • The diagnosis of BAC requires thorough histologic sampling of the tumor.
  • CONCLUSION: Advances in understanding of the pathology and CT features of BAC and adenocarcinoma have led to important changes in diagnostic criteria and classification of BAC and adenocarcinoma.
  • The 2004 WHO classification of adenocarcinoma is readily applicable to research studies, but attention needs to be placed on the relative proportion of the adenocarcinoma subtypes.
  • More work is needed to determine the most important prognostic pathologic features in lung adenocarcinoma.
  • [MeSH-major] Adenocarcinoma, Bronchiolo-Alveolar / classification. Adenocarcinoma, Bronchiolo-Alveolar / pathology. Lung Neoplasms / classification. Lung Neoplasms / pathology
  • [MeSH-minor] Adenocarcinoma / classification. Adenocarcinoma / pathology. Adenocarcinoma / radiography. Biopsy, Needle. Cytodiagnosis / methods. Diagnosis, Differential. Female. Humans. Immunohistochemistry. Male. Risk Factors. Sensitivity and Specificity. Tomography, X-Ray Computed. World Health Organization

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  • (PMID = 17409995.001).
  • [ISSN] 1556-1380
  • [Journal-full-title] Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
  • [ISO-abbreviation] J Thorac Oncol
  • [Language] eng
  • [Publication-type] Consensus Development Conference; Journal Article
  • [Publication-country] United States
  • [Number-of-references] 43
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2. Awaya H, Takeshima Y, Furonaka O, Kohno N, Inai K: Gene amplification and protein expression of EGFR and HER2 by chromogenic in situ hybridisation and immunohistochemistry in atypical adenomatous hyperplasia and adenocarcinoma of the lung. J Clin Pathol; 2005 Oct;58(10):1076-80
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  • [Title] Gene amplification and protein expression of EGFR and HER2 by chromogenic in situ hybridisation and immunohistochemistry in atypical adenomatous hyperplasia and adenocarcinoma of the lung.
  • AIMS: To investigate the importance of gene amplification and EGFR (epidermal growth factor receptor) and HER2 protein expression during the progression of adenocarcinoma of the lung.
  • METHODS: EGFR and HER2 gene amplification was examined in atypical adenomatous hyperplasia (AAH), bronchioloalveolar carcinoma (BAC), and adenocarcinoma with mixed subtypes (MX) by chromogenic in situ hybridisation (CISH), and protein expression was examined by immunohistochemistry using paraffin wax embedded tissues.
  • CONCLUSIONS: EGFR and HER2 gene amplification may be a late event and EGFR and HER2 protein expression may be associated with the development of adenocarcinoma of the lung.
  • [MeSH-major] Adenocarcinoma / genetics. Genes, erbB-2. Lung Neoplasms / genetics. Precancerous Conditions / genetics. Receptor, Epidermal Growth Factor / genetics

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  • (PMID = 16189154.001).
  • [ISSN] 0021-9746
  • [Journal-full-title] Journal of clinical pathology
  • [ISO-abbreviation] J. Clin. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Chromogenic Compounds; EC 2.7.10.1 / Receptor, Epidermal Growth Factor; EC 2.7.10.1 / Receptor, ErbB-2
  • [Other-IDs] NLM/ PMC1770741
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3. Tanaka R, Ishiyama T, Uchihara T, Inadome Y, Iijima T, Morishita Y, Kano J, Goya T, Noguchi M: Expression of the Bax inhibitor-1 gene in pulmonary adenocarcinoma. Cancer; 2006 Feb 1;106(3):648-53
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  • [Title] Expression of the Bax inhibitor-1 gene in pulmonary adenocarcinoma.
  • METHODS: Surgically resected lung specimens were obtained from 32 patients with peripheral adenocarcinomas, and BI-1 gene expression was examined and compared with expression of the p53, bcl-2 and Bax genes.
  • BI-1 gene expression in tumor specimens was significantly higher in adenocarcinomas with bronchioloalveolar carcinoma (BAC) and in adenocarcinomas of mixed subtypes with bronchioloalveolar spreading (14 of 17 tumors; 82.4%) than in carcinomas without it spreading.
  • Patients who had BI-1-positive adenocarcinoma showed a relatively favorable prognosis compared with patients who had BI-1-negative adenocarcinoma.
  • CONCLUSIONS: BI-1 gene expression was restricted to tumor cells with lepidic growth and was a prognostic factor for peripheral-type adenocarcinoma.
  • [MeSH-major] Adenocarcinoma / genetics. Apoptosis / genetics. Lung Neoplasms / genetics. Proteins / analysis

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  • [Copyright] Copyright (c) 2005 American Cancer Society.
  • (PMID = 16353209.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Apoptosis Regulatory Proteins; 0 / Membrane Proteins; 0 / Proteins; 0 / TMBIM6 protein, human
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4. Fujita A, Kameda Y, Goya T: Clinicopathology of stromal invasion in lung adenocarcinoma. Pathol Int; 2009 Jan;59(1):1-6
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  • [Title] Clinicopathology of stromal invasion in lung adenocarcinoma.
  • In the World Health Organization classification, lung adenocarcinoma with mixed subtypes is defined as invasive carcinoma with evidence of vascular, pleural, or stromal invasion.
  • A total of 157 peripheral pure bronchioloalveolar carcinoma (BAC) or lung adenocarcinoma with mixed BAC and others were reviewed.
  • Survival of patients with adenocarcinoma without DAF (n = 41) was 100%.
  • Even when adenocarcinoma involved DAF and lacked EAAI (n = 21), survival was 100%.
  • [MeSH-major] Adenocarcinoma / pathology. Lung Neoplasms / pathology. Neoplasm Invasiveness / pathology

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  • (PMID = 19121086.001).
  • [ISSN] 1440-1827
  • [Journal-full-title] Pathology international
  • [ISO-abbreviation] Pathol. Int.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Australia
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5. Duruisseaux M, Cadranel J, Pérol M, Arpin D: The role of pemetrexed in lung adenocarcinoma, mixed subtype with bronchioloalveolar carcinoma features. Curr Drug Targets; 2010 Jan;11(1):74-7
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  • [Title] The role of pemetrexed in lung adenocarcinoma, mixed subtype with bronchioloalveolar carcinoma features.
  • Bronchioloalveolar carcinoma (BAC) and adenocarcinoma with bronchioloalveolar features (ADC-WBF) belong to the same anatomo-clinical entity and show very similar epidemiologic, clinical and biological characteristics.
  • Pemetrexed has proved to be particularly effective in advanced lung adenocarcinomas and unresectable mesotheliomas, and cases of major and sustained responses of ADC-WBF to pemetrexed have been reported.
  • BAC tumors overexpress FR-alpha, a protein involved in pemetrexed intracellular transport, at rates higher than those observed in lung adenocarcinomas and mesotheliomas and it would seem that pemetrexed efficacy is correlated to FR-alpha expression.
  • [MeSH-major] Adenocarcinoma / drug therapy. Adenocarcinoma, Bronchiolo-Alveolar / drug therapy. Glutamates / therapeutic use. Guanine / analogs & derivatives. Lung Neoplasms / drug therapy

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  • (PMID = 19839924.001).
  • [ISSN] 1873-5592
  • [Journal-full-title] Current drug targets
  • [ISO-abbreviation] Curr Drug Targets
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Glutamates; 04Q9AIZ7NO / Pemetrexed; 5Z93L87A1R / Guanine
  • [Number-of-references] 38
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6. Gamal G, Sano T, Sakurai S, Kawashima O, Sugano M, Nakajima T: Immunohistopathological re-evaluation of adenocarcinoma of the lung with mixed subtypes using a tissue microarray technique and hierarchical clustering analysis. Pathol Int; 2007 Dec;57(12):765-74
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  • [Title] Immunohistopathological re-evaluation of adenocarcinoma of the lung with mixed subtypes using a tissue microarray technique and hierarchical clustering analysis.
  • To re-evaluate adenocarcinoma, mixed subtypes (ADMIX) of the lung, a total of 201 cases were classified into three main subgroups according to the most differentiated histological growth pattern; namely bronchioloalveolar carcinoma (BAC)-mixed, which was the most predominant (73.1%), papillary (PAP)-mixed (21.9%), and acinar-mixed (5%).
  • The PAP-mixed was significantly male predominant and had more progressed clinicopathological features.
  • Hierarchical clustering analysis was separately applied to the immunohistochemical results of ADMIX and ADMIX subgroups, and it was found that most acinar-mixed cases were placed in a separate cluster, while the BAC-mixed and PAP-mixed failed to form significant independent clusters.
  • The antibody clustering profile for the acinar-mixed was clearly different from that for the BAC-mixed or PAP-mixed, but the PAP-mixed shared a dendrogram profile with the other two subgroups.
  • [MeSH-major] Adenocarcinoma / classification. Adenocarcinoma / pathology. Lung Neoplasms / classification. Lung Neoplasms / pathology

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  • (PMID = 17988277.001).
  • [ISSN] 1320-5463
  • [Journal-full-title] Pathology international
  • [ISO-abbreviation] Pathol. Int.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Australia
  • [Chemical-registry-number] 0 / Biomarkers, Tumor
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7. Zakowski MF, Hussain S, Pao W, Ladanyi M, Ginsberg MS, Heelan R, Miller VA, Rusch VW, Kris MG: Morphologic features of adenocarcinoma of the lung predictive of response to the epidermal growth factor receptor kinase inhibitors erlotinib and gefitinib. Arch Pathol Lab Med; 2009 Mar;133(3):470-7
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  • [Title] Morphologic features of adenocarcinoma of the lung predictive of response to the epidermal growth factor receptor kinase inhibitors erlotinib and gefitinib.
  • CONTEXT: A subset of lung adenocarcinomas appears preferentially sensitive to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs).
  • Adenocarcinoma subtypes and morphologic features were defined in histologic and cytologic material.
  • Nonresponders showed more heterogeneous morphology, higher grade, and more subtypes, and were more likely to show solid growth.
  • In nonresponders, the only pure bronchioloalveolar carcinoma was mucinous, a subtype known to be negative for EGFR mutations.
  • Using World Health Organization criteria, all tumors in both groups other than pure bronchioloalveolar carcinomas would be classified as adenocarcinomas, mixed subtype, thereby obscuring some of these distinctions.
  • [MeSH-major] Adenocarcinoma / drug therapy. Adenocarcinoma / pathology. Lung Neoplasms / drug therapy. Lung Neoplasms / pathology. Quinazolines / therapeutic use. Receptor, Epidermal Growth Factor / antagonists & inhibitors

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  • (PMID = 19260752.001).
  • [ISSN] 1543-2165
  • [Journal-full-title] Archives of pathology & laboratory medicine
  • [ISO-abbreviation] Arch. Pathol. Lab. Med.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / R01 CA121210
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Quinazolines; DA87705X9K / Erlotinib Hydrochloride; EC 2.7.10.1 / Receptor, Epidermal Growth Factor; S65743JHBS / gefitinib
  • [Other-IDs] NLM/ NIHMS578987; NLM/ PMC4016915
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8. Rusch VW, Tsuchiya R, Tsuboi M, Pass HI, Grunenwald D, Goldstraw P: Surgery for bronchioloalveolar carcinoma and "very early" adenocarcinoma: an evolving standard of care? J Thorac Oncol; 2006 Nov;1(9 Suppl):S27-31
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  • [Title] Surgery for bronchioloalveolar carcinoma and "very early" adenocarcinoma: an evolving standard of care?
  • Lobectomy and mediastinal lymph node dissection is the standard surgical management of early stage non-small cell lung cancer (NSCLC) because more limited resections have been associated with a higher risk of local recurrence.
  • Nevertheless, recent lung cancer screening studies have led to the detection of an increasing number of "very early" NSCLC (defined as less than 2 cm in size) and of good-prognosis histologic subtypes, bronchioloalveolar carcinoma (BAC), and adenocarcinoma (AC), mixed subtypes that are potentially appropriate for sublobar resection.
  • Very limited experience suggests that lung transplantation leads to prolonged survival in highly selected patients with this histologic subtype.
  • [MeSH-major] Adenocarcinoma, Bronchiolo-Alveolar / mortality. Adenocarcinoma, Bronchiolo-Alveolar / surgery. Lung Neoplasms / mortality. Lung Neoplasms / surgery. Lymph Nodes / pathology. Pneumonectomy / methods
  • [MeSH-minor] Adenocarcinoma / mortality. Adenocarcinoma / pathology. Adenocarcinoma / surgery. Clinical Trials, Phase III as Topic. Early Diagnosis. Female. Humans. Immunohistochemistry. Lymph Node Excision / methods. Male. Mediastinum. Neoplasm Invasiveness / pathology. Neoplasm Staging. Prognosis. Risk Assessment. Survival Analysis. Time Factors. Treatment Outcome

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  • (PMID = 17409998.001).
  • [ISSN] 1556-1380
  • [Journal-full-title] Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
  • [ISO-abbreviation] J Thorac Oncol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 46
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9. Motoi N, Szoke J, Riely GJ, Seshan VE, Kris MG, Rusch VW, Gerald WL, Travis WD: Lung adenocarcinoma: modification of the 2004 WHO mixed subtype to include the major histologic subtype suggests correlations between papillary and micropapillary adenocarcinoma subtypes, EGFR mutations and gene expression analysis. Am J Surg Pathol; 2008 Jun;32(6):810-27
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  • [Title] Lung adenocarcinoma: modification of the 2004 WHO mixed subtype to include the major histologic subtype suggests correlations between papillary and micropapillary adenocarcinoma subtypes, EGFR mutations and gene expression analysis.
  • The histologic heterogeneity of lung adenocarcinoma creates a variety of complex challenges to pathologists in analyzing the various subtypes.
  • Current classification schemas do not take into account the major subtype.
  • We analyzed 100 cases for clinical, pathologic, and molecular features using a modification of the 2004 World Health Organization (WHO) classification to record the major component in the mixed subtype tumors.
  • The most common major histologic subtype was papillary (37%) followed by acinar (30%), solid (25%) and bronchioloalveolar (7%) carcinoma (BAC), although no pure BACs were seen.
  • Papillary adenocarcinoma strongly correlated with EGFR mutation (P<0.001) and gene profile Cluster 1 (P=0.006) with weaker correlations with low grade (P=0.038) and favorable behavior in Stage 1 patients (P=0.047).
  • Micropapillary subtype correlated strongly with EGFR mutation (P<0.001) and weakly with Cluster 1 (P=0.030).
  • Solid adenocarcinoma strongly correlated with gene profile Cluster 3 (P=0.001) and worse survival (P=0.001).
  • Cluster 3 strongly correlated with heavier smoking (P<0.001), larger tumor size (P<0.001), solid subtype (P<0.001), and poor grade (P=0.004); weak correlations were found with KRAS mutation (P=0.025).
  • Higher stage (P<0.001), grade (P<0.001), and solid subtype (P=0.001) correlated with shorter survival.
  • Our data suggest that EGFR mutations are associated with papillary adenocarcinoma and gene profile Cluster 1.
  • We discovered this only because we used a comprehensive approach examining in detail all histologic subtypes and we modified the 2004 WHO mixed subtype to include the major histologic subtype.
  • As we do not know the major genetic pathways of 30% to 70% of lung adenocarcinomas, the comprehensive histologic subtyping we propose gives advantage for recognition of unanticipated histologic-genetic correlations that might not be detected using classification systems that focus primarily on specific aspects of adenocarcinomas such as BAC or EGFR mutations.

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  • (PMID = 18391747.001).
  • [ISSN] 1532-0979
  • [Journal-full-title] The American journal of surgical pathology
  • [ISO-abbreviation] Am. J. Surg. Pathol.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / U01 CA084999; United States / NCI NIH HHS / CA / UO1CA84999
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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10. Jian Z, Tomizawa Y, Yanagitani N, Iijima H, Sano T, Nakajima T: Papillary adenocarcinoma of the lung is a more advanced adenocarcinoma than bronchioloalveolar carcinoma that is composed of two distinct histological subtypes. Pathol Int; 2005 Oct;55(10):619-25
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  • [Title] Papillary adenocarcinoma of the lung is a more advanced adenocarcinoma than bronchioloalveolar carcinoma that is composed of two distinct histological subtypes.
  • To clarify the clinicopathological nature of papillary adenocarcinoma (PA) of the lung, 20 cases of PA were collected consecutively from resected adenocarcinoma of the lung, studied immunohistochemically and, using molecular techniques, compared with bronchioloalveolar carcinoma (BAC).
  • Morphologically, PA was divided into two subtypes according to the presence of residual alveolar structures, detected by elastica van Gieson stain.
  • One of these subtypes was closely related to the morphology of BAC and might be diagnosed as adenocarcinoma with mixed subtypes.
  • The other PA subtype was composed of tall columnar cells and grew compressively, which was similar to type F adenocarcinoma previously reported by Noguchi et al.
  • Immunohistochemical studies using lung tissue-specific antigens, progression markers and tumor suppressor products found that PA seemed a more advanced adenocarcinoma than BAC, but no differences were observed among PA subtypes.
  • Molecular biological analysis using three microsatellite markers at chromosome 3p revealed more frequent loss of heterozygosity in PA than BAC, with no differences among PA subtypes.
  • These findings suggest that PA is a more advanced adenocarcinoma subtype than BAC.
  • Further investigations are needed to clarify true PA as clinicopathologically and biologically independent from other histological subtypes of adenocarcinoma of the lung.
  • [MeSH-major] Adenocarcinoma, Bronchiolo-Alveolar / pathology. Adenocarcinoma, Papillary / pathology. Lung Neoplasms / pathology

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  • (PMID = 16185291.001).
  • [ISSN] 1320-5463
  • [Journal-full-title] Pathology international
  • [ISO-abbreviation] Pathol. Int.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Australia
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / DNA, Neoplasm; 0 / Genetic Markers
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11. Alì G, Donati V, Loggini B, Servadio A, Dell'Omodarme M, Prati MC, Camacci T, Lucchi M, Melfi F, Mussi A, Fontanini G: Different estrogen receptor beta expression in distinct histologic subtypes of lung adenocarcinoma. Hum Pathol; 2008 Oct;39(10):1465-73
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Different estrogen receptor beta expression in distinct histologic subtypes of lung adenocarcinoma.
  • Adenocarcinoma is becoming the most common histologic type of lung cancer in both sex.
  • Several subtypes of lung adenocarcinoma have been recently described with distinct clinicopathologic features and prognostic implications.
  • The purpose of this study is to investigate the role of estrogen receptor beta in lung adenocarcinoma, with particular attention paid to its different histologic subtypes.
  • Nuclear estrogen receptor beta expression was evaluated by immunohistochemistry in 112 lung adenocarcinomas, including both "single subtype" and "mixed subtype" samples.
  • Using a 2-level (high/low) score system, estrogen receptor beta expression was high in most (75%) adenocarcinomas and turned out to be strongly related to the histologic subtypes.
  • In fact, estrogen receptor beta expression was low or negative in 68.2% of solid subtypes, whereas it was high in 76.5% of nonmucinous bronchioloalveolar, in 69.4% of acinar, and in 61.2% of papillary patterns (P = .00004).
  • In conclusion, estrogen receptor beta expression has distinct patterns in lung adenocarcinoma, suggesting a specific role for estrogen receptor beta in the pathogenesis of different histologic subtypes of this type of cancer.
  • Moreover, loss of estrogen receptor beta expression in poorly differentiated (G3) tumors could represent a crucial step in the dedifferentiation process of lung adenocarcinoma.
  • [MeSH-major] Adenocarcinoma / metabolism. Estrogen Receptor beta / metabolism. Lung Neoplasms / metabolism

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  • (PMID = 18620727.001).
  • [ISSN] 1532-8392
  • [Journal-full-title] Human pathology
  • [ISO-abbreviation] Hum. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Estrogen Receptor beta
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12. Maeshima AM, Omatsu M, Tsuta K, Asamura H, Matsuno Y: Immunohistochemical expression of TTF-1 in various cytological subtypes of primary lung adenocarcinoma, with special reference to intratumoral heterogeneity. Pathol Int; 2008 Jan;58(1):31-7
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  • [Title] Immunohistochemical expression of TTF-1 in various cytological subtypes of primary lung adenocarcinoma, with special reference to intratumoral heterogeneity.
  • The immunohistochemical expression of thyroid transcription factor-1 (TTF-1) was investigated in various cytological subtypes of primary lung adenocarcinoma, with special reference to intratumoral heterogeneity.
  • Three groups were categorized according to cytological subtype: group A, adenocarcinomas with either a Clara cell and/or type II epithelial cell component (Clara/type II) or a mixed Clara/type II and bronchial surface epithelial cell component (BSE) (mCB), in addition to other components; group B, adenocarcinomas with components including either BSE, a goblet cell component (GOB) or a mixed BSE and GOB component (mBG), and lacking Clara/type II or mCB; group C, adenocarcinomas with only a poorly differentiated component (POR).
  • [MeSH-major] Adenocarcinoma / metabolism. Adenocarcinoma / pathology. DNA-Binding Proteins / biosynthesis. Lung Neoplasms / metabolism. Lung Neoplasms / pathology

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  • (PMID = 18067638.001).
  • [ISSN] 1320-5463
  • [Journal-full-title] Pathology international
  • [ISO-abbreviation] Pathol. Int.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Australia
  • [Chemical-registry-number] 0 / DNA-Binding Proteins; 0 / TTF1 protein, human
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13. Makimoto Y, Nabeshima K, Iwasaki H, Miyoshi T, Enatsu S, Shiraishi T, Iwasaki A, Shirakusa T, Kikuchi M: Micropapillary pattern: a distinct pathological marker to subclassify tumours with a significantly poor prognosis within small peripheral lung adenocarcinoma (&lt;/=20 mm) with mixed bronchioloalveolar and invasive subtypes (Noguchi's type C tumours). Histopathology; 2005 Jun;46(6):677-84
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Micropapillary pattern: a distinct pathological marker to subclassify tumours with a significantly poor prognosis within small peripheral lung adenocarcinoma (</=20 mm) with mixed bronchioloalveolar and invasive subtypes (Noguchi's type C tumours).
  • AIMS: A micropapillary pattern (MPP) in lung adenocarcinoma, characterized by papillary structures with epithelial tufts lacking a central fibrovascular core, has been reported to be a new pathological marker of poor prognosis.
  • However, its clinicopathological and prognostic significance in small lung adenocarcinomas (</=20 mm) remains undetermined.
  • A new histological classification of small lung adenocarcinoma proposed by Noguchi et al. has been found to be useful since it has defined surgically curable bronchioloalveolar carcinoma (BAC)-type tumours (Noguchi's type A and B) based on the absence of active fibroblastic proliferation.
  • However, BAC-type tumours with active fibroblastic proliferation (Noguchi's type C), which is adenocarcinoma with mixed subtypes including BAC and invasive carcinoma in the new World Health Organization (WHO) classification, account for most of the small adenocarcinomas and represent a heterogeneous group ranging from minimal to overtly invasive cancer with variable prognoses.
  • Therefore, in this study the aim was to investigate whether MPP can be an additional histological marker(s) to subclassify this heterogeneous group in small lung adenocarcinoma.
  • METHODS AND RESULTS: One hundred and twenty-two cases of small lung adenocarcinomas (</=20 mm in maximum dimension) classified according to the new WHO classification and Noguchi's proposal were analysed with reference to the presence of MPP.
  • The 5-year survival rates of BAC (Noguchi's type A and B) (n=14), mixed BAC and invasive adenocarcinoma (Noguchi's type C) (n=85) and invasive adenocarcinoma (Noguchi's type D and F) (n=23) were 100%, 68% and 36%, respectively.
  • In patients with mixed BAC and invasive adenocarcinoma (Noguchi's type C tumours), the 5-year survival of the MPP-positive group (n=51) was 54%, significantly lower than that of the MPP-negative group (n=23) of 100% (P=0.02).
  • CONCLUSIONS: MPP is a simple and distinct pathological marker to subclassify tumours with a significantly poor prognosis within small (</=20 mm) mixed BAC and invasive adenocarcinoma (Noguchi's type C tumours).
  • [MeSH-major] Adenocarcinoma, Bronchiolo-Alveolar / pathology. Adenocarcinoma, Papillary / pathology. Lung Neoplasms / pathology

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  • (PMID = 15910599.001).
  • [ISSN] 0309-0167
  • [Journal-full-title] Histopathology
  • [ISO-abbreviation] Histopathology
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
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14. Chilosi M, Murer B: Mixed adenocarcinomas of the lung: place in new proposals in classification, mandatory for target therapy. Arch Pathol Lab Med; 2010 Jan;134(1):55-65
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Mixed adenocarcinomas of the lung: place in new proposals in classification, mandatory for target therapy.
  • CONTEXT: Lung cancer is one of the most frequent and lethal malignant neoplasms, but knowledge regarding the molecular basis of its pathogenesis is far from complete due to the striking diversity of different forms.
  • The current lung cancer classification (World Health Organization 2004) can efficiently distinguish clinically relevant major subtypes (small cell and non-small cell carcinomas), but its results are partly inadequate when facing prognostic and therapeutic decisions for non-small cell carcinomas, especially for the group of tumors classified as adenocarcinoma.
  • Lung adenocarcinoma comprises a heterogeneous group of tumors characterized by diverse morphologic features and molecular pathogenesis.
  • The category of mixed adenocarcinomas includes most adenocarcinomas (approximately 80%) and, according to World Health Organization criteria, is defined by the occurrence of a mixed array of different patterns (acinar, papillary, bronchioloalveolar, solid with mucin).
  • The histologic recognition of mixed adenocarcinoma is subjective and cannot consistently discriminate between responders and nonresponders to new targeted therapies (eg, tyrosine kinase inhibitors).
  • In this evolving scenario, pathologists face new challenging diagnostic roles that include not only the precise morphologic definition of carcinoma subtypes but also their molecular characterization.
  • OBJECTIVE: To use a comprehensive critical analysis reconciling the overwhelming variety of biologic, morphologic, molecular, and clinical data to define new classification schemes for lung adenocarcinoma.
  • CONCLUSIONS: A new classification approach should redefine lung adenocarcinoma heterogeneity reconciling classic morphology, immunophenotypic and molecular features of neoplastic cells, and also relevant information provided by stem cell biology.
  • This approach, which has been already successfully applied in World Health Organization classification of other tumors, could improve the recognition of new reproducible profiles for adenocarcinomas, more closely and reproducibly related to clinical features and response to specific therapies, limiting the use of "wastebasket" categories such as mixed adenocarcinoma.
  • [MeSH-major] Adenocarcinoma / classification. Adenocarcinoma / pathology. Lung Neoplasms / classification. Lung Neoplasms / pathology

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  • (PMID = 20073606.001).
  • [ISSN] 1543-2165
  • [Journal-full-title] Archives of pathology & laboratory medicine
  • [ISO-abbreviation] Arch. Pathol. Lab. Med.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor
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15. Tanaka R, Horikoshi H, Nakazato Y, Seki E, Minato K, Iijima M, Kojima M, Goya T: Magnetic resonance imaging in peripheral lung adenocarcinoma: correlation with histopathologic features. J Thorac Imaging; 2009 Feb;24(1):4-9
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  • [Title] Magnetic resonance imaging in peripheral lung adenocarcinoma: correlation with histopathologic features.
  • OBJECTIVE: Magnetic resonance imaging (MRI) with various technologic advancements has generally been used to elevate the accuracy of diagnosis for several malignant tumors.
  • This study retrospectively evaluated the efficacy of newer MRI techniques for differentiating among the different types of invasiveness in lung adenocarcinoma by comparing the MRI findings with the pathologic findings.
  • MATERIALS AND METHODS: From May 2005 to April 2007, 46 patients with lung adenocarcinoma measuring 3 cm or less across the greatest dimension underwent a surgical operation including preoperative MRI study in this hospital.
  • RESULTS: Of all the tumors, 13 were bronchioloalveolar carcinoma (BAC), 24 were adenocarcinomas with mixed subtypes (advanced BAC), and 9 were other histologic subtypes (non-BAC).
  • CONCLUSIONS: DWI could therefore be a useful diagnostic modality for differentiating the subtypes of lung adenocarcinomas, and the MRI finding may thus provide useful supplementary information before surgery comprising limited resections.
  • [MeSH-major] Adenocarcinoma / pathology. Lung Neoplasms / pathology. Magnetic Resonance Imaging / methods

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  • (PMID = 19242296.001).
  • [ISSN] 1536-0237
  • [Journal-full-title] Journal of thoracic imaging
  • [ISO-abbreviation] J Thorac Imaging
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Contrast Media; K2I13DR72L / Gadolinium DTPA
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16. Stoehlmacher J, Goekkurt E, Hoeffken G, Zinsky R, Lynch F, Buettner H, Scheil-Bertram S, Schirren J, Ehninger G, Fisseler-Eckhoff A: Thymidylate synthase polymorphisms and immunohistochemistry in non-small cell lung cancer. J Clin Oncol; 2009 May 20;27(15_suppl):11101

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  • [Title] Thymidylate synthase polymorphisms and immunohistochemistry in non-small cell lung cancer.
  • : 11101 Background: Recently, pemetrexed has been introduced into the treatment of non-small cell lung cancer (NSCLC).
  • There's evidence that pemetrexed appears to be more efficient in non squamous NSCLC including adenocarcinoma (AC) and large cell carcinoma (LCC).
  • Distribution of histology was as follows: 50% AC, 42% squamous cell carcinoma (SCC), 3% LCC and 5% mixed or other histological subtypes.
  • There was no significant difference between histological subtypes of NSCLC with respect to TS protein expression.
  • CONCLUSIONS: TS polymorphisms are significantly associated with histology subtypes in NSCLC.

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  • (PMID = 27963465.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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17. Davidson JA, Wong V, Fraser R, Hirsh V: Comparison of primary tumor maximal standardized uptake value (SUV&lt;sub&gt;max&lt;/sub&gt;) on preoperative [18F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and histological subtype in patients with non-small cell lung cancer (NSCLC). J Clin Oncol; 2009 May 20;27(15_suppl):7571

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Comparison of primary tumor maximal standardized uptake value (SUV<sub>max</sub>) on preoperative [18F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and histological subtype in patients with non-small cell lung cancer (NSCLC).
  • The SUV<sub>max</sub> is a semiquantitative measure of metabolic activity that can distinguish benign from malignant tissue but published data are conflicting regarding its ability to discriminate between major histological subtypes.
  • Only patients with Adenocarcinoma (AC), Squamous Cell carcinoma (SC), or Large Cell carcinoma (LC), and definitive pathological staging, were included.
  • The SUV<sub>max</sub> values for each histological subtype, along with primary tumor sizes, were compared using F test and t-test analyses.
  • RESULTS: The 15 patients with SC and 5 with LC histology were found to have significantly greater preoperative SUV<sub>max</sub> values than the 19 patients with AC (mean 12.7 and 17.2 vs. 9.4, respectively, P < 0.05), despite the fact that no significant differences in tumor size were observed between histological subtypes.
  • This finding may be helpful in the future when sufficient tissue cannot be obtained for pathological diagnosis or to identify the predominant pathology of mixed tumors.

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  • (PMID = 27963356.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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18. Luttgen MS, Marrinucci D, Lazar D, Malchiodi M, Clark P, Huynh E, Bethel K, Bazhenova L, Nieva J, Kuhn P: Circulating tumor cells monitored over time in lung cancer patients. J Clin Oncol; 2009 May 20;27(15_suppl):11025

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  • [Title] Circulating tumor cells monitored over time in lung cancer patients.
  • While many current techniques employ immunomagnetic-enrichment based protocols focused on the importance of a particular CTC number as the indicator of patient status or outcome, we employ a cytometric, enrichment free approach using an immunofluorescent protocol to monitor CTC counts in patients with non-small cell lung cancer (NSCLC) over the course of treatment.
  • The histological subtypes in the 42 cases for which the data was available included adenocarcinoma (22/42), squamous cell carcinoma (6/42), large cell undifferentiated carcinoma (3/42), and non-small cell lung carcinoma not further described, poorly differentiated, or with a mixed pattern (11/42).

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  • (PMID = 27963968.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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19. Sun JS, Park KJ, Sheen SS, Yoon JK, Yoon SN, Lee KB, Hwang SC: Clinical usefulness of the fluorodeoxyglucose (FDG)-PET maximal standardized uptake value (SUV) in combination with CT features for the differentiation of adenocarcinoma with a bronchioloalveolar carcinoma from other subtypes of non-small cell lung cancers. Lung Cancer; 2009 Nov;66(2):205-10
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  • [Title] Clinical usefulness of the fluorodeoxyglucose (FDG)-PET maximal standardized uptake value (SUV) in combination with CT features for the differentiation of adenocarcinoma with a bronchioloalveolar carcinoma from other subtypes of non-small cell lung cancers.
  • PURPOSE: To evaluate the clinical usefulness of fluorodeoxyglucose (FDG)-PET maximal SUV in combination with CT features for differentiation of adenocarcinoma with bronchioloalveolar carcinoma (BAC) from other subtypes of non-small cell lung cancer (NSCLC).
  • We categorized NSCLC into adenocarcinoma with BAC feature and other subtypes.
  • Finally, there were 16 cases of adenocarcinoma with BAC and 109 cases of other NSCLC subtypes included in the study.
  • Several CT features of lung cancer were analyzed, including tumor size, presence of spiculation, margin (irregular or smooth), pattern of the mass (pure solid, pure ground glass opacity and mixed), associated pleural effusion and location (center, mid and periphery).
  • The diagnostic performances of CT alone, PET alone, and combination of two modalities to predict adenocarcinoma with BAC from other subtypes of NSCLC were calculated.
  • RESULTS: A nodule with a mixed pattern with partly solid and ground glass opacity was significantly more frequent CT feature of an adenocarcinoma with BAC (8/16, 50%) as compared with the other subtypes (2/109, 1.8%) (p<0.0001).
  • Maximal SUV of adenocarcinoma with BAC (mean=7.2) was significantly lower than that of other subtypes of NSCLC (mean=13.33) (p<0.0001).
  • Sensitivity, specificity, PPV, and NPV of CT for differentiating adenocarcinoma with BAC from other subtypes was 50% (8/16), 98.2% (107/109), 80% (8/10), and 93% (107/115), respectively.
  • CONCLUSION: Careful combined assessment of the FDG-PET maximal SUV and CT findings have the potential to differentiate an adenocarcinoma with BAC from other NSCLC subtypes, such as a pure BAC.
  • [MeSH-major] Adenocarcinoma / diagnosis. Adenocarcinoma, Bronchiolo-Alveolar / diagnosis. Carcinoma, Non-Small-Cell Lung / diagnosis. Fluorodeoxyglucose F18. Lung Neoplasms / diagnosis. Positron-Emission Tomography / methods. Tomography, X-Ray Computed / methods

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  • (PMID = 19203812.001).
  • [ISSN] 1872-8332
  • [Journal-full-title] Lung cancer (Amsterdam, Netherlands)
  • [ISO-abbreviation] Lung Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Ireland
  • [Chemical-registry-number] 0Z5B2CJX4D / Fluorodeoxyglucose F18
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20. Tsuta K, Ishii G, Nitadori J, Murata Y, Kodama T, Nagai K, Ochiai A: Comparison of the immunophenotypes of signet-ring cell carcinoma, solid adenocarcinoma with mucin production, and mucinous bronchioloalveolar carcinoma of the lung characterized by the presence of cytoplasmic mucin. J Pathol; 2006 May;209(1):78-87
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  • [Title] Comparison of the immunophenotypes of signet-ring cell carcinoma, solid adenocarcinoma with mucin production, and mucinous bronchioloalveolar carcinoma of the lung characterized by the presence of cytoplasmic mucin.
  • The latest World Health Organization (WHO) classification divides adenocarcinoma mainly into adenocarcinoma mixed subtypes, acinar adenocarcinoma, papillary adenocarcinoma, bronchioloalveolar carcinoma, and solid adenocarcinoma with mucin production, and it mentions several variants, including fetal adenocarcinoma, mucinous ("colloid") adenocarcinoma, mucinous cystadenocarcinoma, signet-ring adenocarcinoma, and clear cell adenocarcinoma.
  • In general, the mucin-producing adenocarcinoma of the lung comprises signet-ring cell carcinoma (SRCC), solid adenocarcinoma with mucin production (SA), and mucinous bronchioloalveolar carcinoma (m-BAC), mucinous ("colloid") adenocarcinomas and/or mucinous cystadenocarcinoma, and mucoepidermoid carcinoma.
  • In this study we analysed SRCC, SA, m-BAC, normal lung, and foregut-related secretory tissue for immunohistochemical differences using tissue microarrays.
  • These immunohistochemical findings support the results of our previous clinicopathological analysis of SRCC of the lung showing that SRCC occurs anatomically in the peripheral portion of the lung rather than in the bronchial gland-bearing portion.
  • [MeSH-major] Adenocarcinoma / immunology. Lung Neoplasms / immunology. Mucins / metabolism. Neoplasm Proteins / metabolism
  • [MeSH-minor] Adenocarcinoma, Bronchiolo-Alveolar / immunology. Adenocarcinoma, Bronchiolo-Alveolar / metabolism. Adenocarcinoma, Mucinous / immunology. Adenocarcinoma, Mucinous / metabolism. Carcinoma, Signet Ring Cell / immunology. Carcinoma, Signet Ring Cell / metabolism. Humans. Immunoenzyme Techniques. Immunophenotyping. Protein Array Analysis / methods

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  • [Copyright] Copyright 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
  • (PMID = 16463270.001).
  • [ISSN] 0022-3417
  • [Journal-full-title] The Journal of pathology
  • [ISO-abbreviation] J. Pathol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Mucins; 0 / Neoplasm Proteins
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21. Prior JO, Stupp R, Christodoulou M, Letovanec I: Micropapillary pattern in lung adenocarcinoma: aspect on 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Interact Cardiovasc Thorac Surg; 2010 Jan;10(1):144-5
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  • [Title] Micropapillary pattern in lung adenocarcinoma: aspect on 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging.
  • We diagnosed a non-small cell lung carcinoma in a 49-year-old female patient with the histopathological diagnosis of stage IIIB mixed bronchioloalveolar and papillary adenocarcinoma with extensive micropapillary feature, which was not visualized on the preoperative multimodality imaging with positron emission tomography (PET) and computed tomography (CT).
  • The micropapillary component characterized by a unique growth pattern with particular morphological features can be observed in all subtypes of lung adenocarcinoma.
  • [MeSH-major] Adenocarcinoma, Papillary / diagnosis. Carcinoma, Non-Small-Cell Lung / diagnosis. Fluorodeoxyglucose F18. Lung Neoplasms / diagnosis. Positron-Emission Tomography. Radiopharmaceuticals. Tomography, X-Ray Computed

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  • (PMID = 19875512.001).
  • [ISSN] 1569-9285
  • [Journal-full-title] Interactive cardiovascular and thoracic surgery
  • [ISO-abbreviation] Interact Cardiovasc Thorac Surg
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Phytogenic; 0 / Radiopharmaceuticals; 0Z5B2CJX4D / Fluorodeoxyglucose F18
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22. Luo DL, Liu YH, Zhuang HG, Liao RQ, Luo XL, Xu FP, Zhang F: [Clinicopathologic study of pulmonary adenocarcinoma with features of bronchioloalveolar carcinoma]. Zhonghua Bing Li Xue Za Zhi; 2008 Nov;37(11):737-42
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  • [Title] [Clinicopathologic study of pulmonary adenocarcinoma with features of bronchioloalveolar carcinoma].
  • (1) BAC of strictly defined, (2) adenocarcinoma with bronchioloalveolar features, (3) other different histologic subtypes of lung adenocarcinomas.
  • METHODS: Surgical specimens from 348 lung adenocarcinoma patients admitted in that hospital between 1998 - 2005 were included.
  • RESULTS: The resected lung adenocarcinomas consisted of different histologic subtypes.
  • The most frequent one was adenocarcinoma of mixed subtypes (78.2%, 272/348), followed by the acinar type (8.1%, 28/348), the papillary type (4.0%, 14/348), the BAC (3.7%, 13/348), the mucinous (colloid) type (3.4%, 12/348) and the solid types (2.3%, 8/348).
  • The fetal adenocarcinoma was the least component detected.
  • [MeSH-major] Adenocarcinoma / pathology. Adenocarcinoma, Bronchiolo-Alveolar / pathology. Kaplan-Meier Estimate. Lung Neoplasms / pathology. Survival Rate
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Female. Humans. Lung / pathology. Male. Middle Aged. Neoplasm Staging / methods. Prognosis

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  • (PMID = 19094707.001).
  • [ISSN] 0529-5807
  • [Journal-full-title] Zhonghua bing li xue za zhi = Chinese journal of pathology
  • [ISO-abbreviation] Zhonghua Bing Li Xue Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
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23. Wang Y, Liu XG, Liang MZ, Qin PX, Lin YJ, Yi XP: [Correlation of early phase contrast enhancement of multi-detector row computed tomography to tumor stroma of nodular solid lung adenocarcinoma]. Ai Zheng; 2008 Nov;27(11):1190-6
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  • [Title] [Correlation of early phase contrast enhancement of multi-detector row computed tomography to tumor stroma of nodular solid lung adenocarcinoma].
  • BACKGROUND & OBJECTIVE: Dynamic enhanced multi-detector row CT (MDCT) has been used in differential diagnosis of pulmonary nodules, but its mechanism was unclear yet.
  • This study was to evaluate the correlations of early phase enhancement of MDCT to proportion and distribution of stroma in solid lung adenocarcinoma.
  • METHODS: A total of 31 patients with lung adenocarcinoma underwent routine contrast-enhanced MDCT.
  • Of the 31 nodules, 18 (58.1%) showed homogenous enhancement, 10 (32.3%) showed peripheral inhomogenous enhancement, 1 (3.2%) showed central inhomogenous enhancement, 1 (3.2%) showed asymmetrical inhomogenous enhancement, 1 (3.2%) showed no enhancement; 18 (58.1%) nodules showed mixed distribution of stroma, 11 (35.5%) showed peripheral distribution, 1 (3.2%) showed central distribution, 1 (3.2%) showed asymmetrical distribution.
  • Most acinar adenocarcinomas had net enhancement of > 20 Hu, which was significantly higher than that of solid adenocarcinomas with mucin subtype (P=0.005).
  • CONCLUSIONS: Extent and pattern of CT enhancement of solid lung adenocarcinoma nodules reflect the proliferation and distribution of stroma, respectively.
  • It is helpful to comprehend some false negative on CT enhancement by adequately understanding of the pathologic features of different subtypes of lung adenocarcinoma.
  • [MeSH-major] Adenocarcinoma / radiography. Lung Neoplasms / radiography. Solitary Pulmonary Nodule / radiography. Tomography, Spiral Computed / methods
  • [MeSH-minor] Adenocarcinoma, Papillary / pathology. Adenocarcinoma, Papillary / radiography. Adult. Aged. Carcinoma, Acinar Cell / pathology. Carcinoma, Acinar Cell / radiography. Female. Humans. Male. Microvessels / pathology. Microvessels / radiography. Middle Aged. Neoplasm Invasiveness. Neoplasm Staging. Radiographic Image Enhancement

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  • (PMID = 19000452.001).
  • [Journal-full-title] Ai zheng = Aizheng = Chinese journal of cancer
  • [ISO-abbreviation] Ai Zheng
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
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24. Sakao Y, Miyamoto H, Sakuraba M, Oh T, Shiomi K, Sonobe S, Izumi H: Prognostic significance of a histologic subtype in small adenocarcinoma of the lung: the impact of nonbronchioloalveolar carcinoma components. Ann Thorac Surg; 2007 Jan;83(1):209-14
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  • [Title] Prognostic significance of a histologic subtype in small adenocarcinoma of the lung: the impact of nonbronchioloalveolar carcinoma components.
  • BACKGROUND: We tried to clarify whether the histologic subtypes and the size of the solid component of an adenocarcinoma are more important predictive factors for invasiveness or prognosis than is total tumor size, even in lung adenocarcinomas that were 2 cm or smaller.
  • METHODS: Between 1996 and December 2005, after standard surgical treatment, 82 patients were diagnosed as having adenocarcinoma with a maximum diameter of 2 cm or less.
  • Histologic subtype was classified into two groups: mixed BAC (mixed adenocarcinoma with BAC) and minimal or non-BAC (tumors with little or no BAC component).
  • RESULTS: Histologic subtype was a significant predictive factor both for invasiveness (vascular or lymph vessels) and lymph node metastasis, in both univariate and multivariate analysis.
  • However, diameter excluding the BAC component was a significant factor for invasiveness in mixed BAC type (p = 0.035), whereas total diameter was not significant (p = 0.28).
  • Finally, histologic subtype and lymph node metastasis were significant prognostic factors for survival in both univariate (p = 0.03, 0.05, respectively) and multivariate (p = 0.04, 0.05, respectively) analyses.
  • The 5-year survival rate was 94.4% (94.1% for pN0) for the mixed BAC type and 71.4% (78.7% for pN0) for the minimal or non-BAC type (p = 0.009; p = 0.04 for pN0 nodes).
  • The first category is a minimal or non-BAC adenocarcinoma that shows aggressive biological behavior.
  • The second category is a mixed BAC, which demonstrates less invasive or aggressive biological behavior than the minimal or non-BAC type, with the degree of invasiveness being associated with the size of the non-BAC component.
  • [MeSH-major] Adenocarcinoma / classification. Adenocarcinoma, Bronchiolo-Alveolar / classification. Lung Neoplasms / classification

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  • [CommentIn] Ann Thorac Surg. 2007 Jan;83(1):214-5 [17184665.001]
  • (PMID = 17184664.001).
  • [ISSN] 1552-6259
  • [Journal-full-title] The Annals of thoracic surgery
  • [ISO-abbreviation] Ann. Thorac. Surg.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Netherlands
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25. Awaya H, Takeshima Y, Amatya VJ, Ishida H, Yamasaki M, Kohno N, Inai K: Loss of expression of E-cadherin and beta-catenin is associated with progression of pulmonary adenocarcinoma. Pathol Int; 2005 Jan;55(1):14-8
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  • [Title] Loss of expression of E-cadherin and beta-catenin is associated with progression of pulmonary adenocarcinoma.
  • The aim of the present study was to determine the association of loss of membranous expression of epithelial (E)-cadherin and beta-catenin with the progression of pulmonary adenocarcinoma.
  • The expression of E-cadherin and beta-catenin was examined in 154 cases of pulmonary adenocarcinoma, including 49 cases of atypical adenomatous hyperplasia (AAH), 40 cases of bronchioloalveolar carcinoma (BAC), 42 cases of BAC-dominant type of adenocarcinoma with mixed subtypes (early MX) and 23 cases of BAC-recessive type of adenocarcinoma with mixed subtypes (overt MX), by immunohistochemistry.
  • Loss of expression of E-cadherin and beta-catenin may play an important role in the progression of pulmonary adenocarcinoma, and these events occur before structural destruction of the alveolar wall by invasion of carcinoma cell.
  • [MeSH-major] Adenocarcinoma / metabolism. Adenocarcinoma / pathology. Cadherins / biosynthesis. Cytoskeletal Proteins / biosynthesis. Lung Neoplasms / metabolism. Lung Neoplasms / pathology. Trans-Activators / biosynthesis

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  • (PMID = 15660698.001).
  • [ISSN] 1320-5463
  • [Journal-full-title] Pathology international
  • [ISO-abbreviation] Pathol. Int.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Australia
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / CTNNB1 protein, human; 0 / Cadherins; 0 / Cytoskeletal Proteins; 0 / Trans-Activators; 0 / beta Catenin
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26. Dacic S: Minimally invasive adenocarcinomas of the lung. Adv Anat Pathol; 2009 May;16(3):166-71
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  • [Title] Minimally invasive adenocarcinomas of the lung.
  • Current World Health Organization (WHO) classification of lung adenocarcinomas includes noninvasive bronchioloalveolar carcinoma (BAC) and several patterns of invasive adenocarcinoma.
  • The most common is a mixed subtype of adenocarcinoma.
  • This group is very heterogenous and includes a wide spectrum of tumors ranging from adenocarcinomas with a dominant BAC growth pattern (lepidic growth) to frankly invasive adenocarcinoma with no BAC component.
  • The change in WHO definition of BAC and introduction of mixed subtype of adenocarcinoma resulted in disconnect between surgical pathologists and clinicians regarding the use of terminology and criteria for diagnosis of BAC and mixed subtype of adenocarcinoma.
  • It is clear that pure BAC is an extremely rare tumor, whereas mixed subtypes of adenocarcinomas may have various clinical presentations and outcomes.
  • The mounting evidence suggests that a subset of mixed subtype of adenocarcinomas with areas of BAC and focal invasion probably represent more indolent tumors.
  • On the basis of the published data, there is a proposal to define a subcategory of "minimally invasive adenocarcinoma" of the lung.
  • [MeSH-major] Adenocarcinoma / pathology. Adenocarcinoma, Bronchiolo-Alveolar / pathology. Lung Neoplasms / pathology. Mixed Tumor, Malignant / pathology

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  • (PMID = 19395880.001).
  • [ISSN] 1533-4031
  • [Journal-full-title] Advances in anatomic pathology
  • [ISO-abbreviation] Adv Anat Pathol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 32
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27. Rapa I, Volante M, Cappia S, Rosas R, Scagliotti GV, Papotti M: Cathepsin K is selectively expressed in the stroma of lung adenocarcinoma but not in bronchioloalveolar carcinoma. A useful marker of invasive growth. Am J Clin Pathol; 2006 Jun;125(6):847-54
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  • [Title] Cathepsin K is selectively expressed in the stroma of lung adenocarcinoma but not in bronchioloalveolar carcinoma. A useful marker of invasive growth.
  • Lung bronchioalveolar carcinomas (BACs) are noninvasive tumors showing lepidic growth and excellent prognosis, whereas all the other variants of adenocarcinoma are invasive tumors with a worse prognosis.
  • The identification of minimal invasive foci in adenocarcinoma, therefore, is of prognostic relevance.
  • A series of 68 pulmonary tumors, including 40 acinar/papillary adenocarcinomas, 18 adenocarcinomas of the mixed subtype, and 10 BACs was tested by immunohistochemical analysis for cathepsin K expression, a proteinase involved in bone and extracellular matrix remodeling.
  • Our findings suggest pathogenetic implications of cathepsin K in the mechanisms of tumor invasiveness in lung carcinoma; in addition, cathepsin K immunodetection may be a valuable adjunct in the correct classification of pulmonary adenocarcinomas, especially in small sclerosing BACs and mixed adenocarcinoma subtypes with minimal infiltrative growth.
  • [MeSH-major] Adenocarcinoma / enzymology. Adenocarcinoma, Bronchiolo-Alveolar / enzymology. Cathepsins / metabolism. Lung Neoplasms / enzymology

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  • (PMID = 16690483.001).
  • [ISSN] 0002-9173
  • [Journal-full-title] American journal of clinical pathology
  • [ISO-abbreviation] Am. J. Clin. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; EC 3.4.- / Cathepsins; EC 3.4.22.38 / CTSK protein, human; EC 3.4.22.38 / Cathepsin K
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28. Al-Salam S, Al-Ashari M: Expression of Galectin-3, CD138, p16INK4a, and TTF-1 in mucinous bronchioloalveolar adenocarcinoma after Hodgkin lymphoma. Appl Immunohistochem Mol Morphol; 2009 Jul;17(4):351-6
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  • [Title] Expression of Galectin-3, CD138, p16INK4a, and TTF-1 in mucinous bronchioloalveolar adenocarcinoma after Hodgkin lymphoma.
  • Bronchioloalveolar carcinoma (BAC) is a subset of lung adenocarcinoma that has a distinct clinical presentation, tumor biology, response to therapy, and prognosis compared with other subtypes of non-small-cell lung carcinoma.
  • Microscopically, BACs have been divided into mucinous, nonmucinous, and mixed types.
  • We describe a case of young female who received radiation therapy to the mediastinum and chemotherapy for Hodgkin lymphoma and now develops mucinous bronchioalveolar adenocarcinoma of the left lung which to the best of our knowledge has not been previously described after radiotherapy and chemotherapy for Hodgkin lymphoma.

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  • (PMID = 18997617.001).
  • [ISSN] 1533-4058
  • [Journal-full-title] Applied immunohistochemistry & molecular morphology : AIMM
  • [ISO-abbreviation] Appl. Immunohistochem. Mol. Morphol.
  • [Language] ENG
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Cyclin-Dependent Kinase Inhibitor p16; 0 / Galectin 3; 0 / Neoplasm Proteins; 0 / Nuclear Proteins; 0 / SDC1 protein, human; 0 / Syndecan-1; 0 / Transcription Factors; 0 / thyroid nuclear factor 1
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29. Raz DJ, Zell JA, Karnezis AN, Odisho A, Ignatius Ou SH, Anton-Culver H, Jablons DM: Misclassification of bronchioloalveolar carcinoma with cytologic diagnosis of lung cancer. J Thorac Oncol; 2006 Nov;1(9):943-8
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  • [Title] Misclassification of bronchioloalveolar carcinoma with cytologic diagnosis of lung cancer.
  • INTRODUCTION: Cytology is commonly used to diagnose non-small cell lung cancer (NSCLC) but is an inaccurate means of diagnosis of bronchioloalveolar carcinoma (BAC).
  • The aims of this study were to calculate the sensitivity and specificity of cytologic diagnosis of BAC and to estimate the misclassification of BAC as other subtypes of NSCLC.
  • METHODS: Preoperative fine-needle aspiration cytology diagnoses were compared to histology diagnoses in 222 patients, including 51 patients with pure or mixed BAC, who underwent lung resection for NSCLC at our institution since 1999.
  • RESULTS: The sensitivity and specificity of a cytologic diagnosis of BAC were 12% and 99%, respectively.
  • Based on cytologic diagnosis, 63% of BAC was misclassified as adenocarcinoma, and 18% was misclassified as undifferentiated NSCLC.
  • CONCLUSIONS: Diagnosis of NSCLC by cytology alone results in significant misclassification of BAC, most commonly as adenocarcinoma or undifferentiated NSCLC.
  • Because patients with BAC respond differently to certain treatments such as endothelial growth factor receptor inhibitors and surgical resection of multifocal lung cancer, misclassification of BAC may have important therapeutic implications.
  • [MeSH-major] Adenocarcinoma, Bronchiolo-Alveolar / pathology. Carcinoma, Non-Small-Cell Lung / pathology. Lung Neoplasms / pathology
  • [MeSH-minor] Adult. Aged. Biopsy, Fine-Needle. Cohort Studies. Cytodiagnosis / classification. Diagnosis, Differential. Female. Humans. Immunohistochemistry. Male. Middle Aged. Neoplasm Staging. Preoperative Care / methods. Probability. Retrospective Studies. Risk Assessment. Sensitivity and Specificity

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  • (PMID = 17409976.001).
  • [ISSN] 1556-1380
  • [Journal-full-title] Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
  • [ISO-abbreviation] J Thorac Oncol
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / R01 CA093708-04; United States / NCI NIH HHS / CA / R01 CA093708-02; United States / NCI NIH HHS / CA / R01 CA093708; United States / NCI NIH HHS / CA / T32 CA108462; United States / NCI NIH HHS / CA / T32 CA108462-01
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] United States
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30. Furonaka O, Takeshima Y, Awaya H, Kushitani K, Kohno N, Inai K: Aberrant methylation and loss of expression of O-methylguanine-DNA methyltransferase in pulmonary squamous cell carcinoma and adenocarcinoma. Pathol Int; 2005 Jun;55(6):303-9
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  • [Title] Aberrant methylation and loss of expression of O-methylguanine-DNA methyltransferase in pulmonary squamous cell carcinoma and adenocarcinoma.
  • The methylation status of the MGMT gene was investigated by methylation-specific polymerase chain reaction (PCR) and expression status was investigated by immunohistochemistry in 70 cases of pulmonary squamous cell carcinoma (pulmonary SqCC), including 23 cases of the central type and 47 cases of the peripheral type, and in 53 cases of the peripheral type of pulmonary adenocarcinoma (AC).
  • In AC with mixed subtypes showing MGMT methylation, the level of MGMT expression in the bronchioloalveolar carcinoma (BAC) area (non-invasive status) was significantly higher than that in the papillary or acinar AC area (invasive status; P = 0.0002).
  • This trend was not found in AC with mixed subtypes showing no MGMT methylation (P = 0.10).
  • [MeSH-major] Adenocarcinoma / pathology. Carcinoma, Squamous Cell / pathology. DNA Methylation. Lung Neoplasms / pathology. O(6)-Methylguanine-DNA Methyltransferase / genetics

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  • (PMID = 15943786.001).
  • [ISSN] 1320-5463
  • [Journal-full-title] Pathology international
  • [ISO-abbreviation] Pathol. Int.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Australia
  • [Chemical-registry-number] 0 / DNA, Neoplasm; EC 2.1.1.63 / O(6)-Methylguanine-DNA Methyltransferase
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31. Matsuoka T, Fukamitsu G, Onoda M, Uesugi N, Kawano K, Katou T: [Synchronous multiple lung cancer including a lesion with a thin-walled cavity; report of a case]. Kyobu Geka; 2010 Feb;63(2):164-7
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  • [Title] [Synchronous multiple lung cancer including a lesion with a thin-walled cavity; report of a case].
  • A 79-year-old woman underwent video-assisted thoracic surgery (VATS)-left S6 segmentectomy for left lung cancer (papillary adenocarcinoma, pT1N0M0, stage IA), and were followed-up at our hospital.
  • CT-guided biopsy revealed well differentiated adenocarcinoma VATS-right upper lobectomy was performed and both lesions were diagnosed as "adenocarcinoma with mixed subtypes (BAC : acinar type), synchronous multiple lung cancer one of which formed thin-walled cavity" histopathologically.
  • [MeSH-major] Adenocarcinoma, Papillary / surgery. Lung Neoplasms / surgery. Neoplasms, Multiple Primary / surgery

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  • (PMID = 20141088.001).
  • [ISSN] 0021-5252
  • [Journal-full-title] Kyobu geka. The Japanese journal of thoracic surgery
  • [ISO-abbreviation] Kyobu Geka
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
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32. Goto T, Maeshima A, Oyamada Y, Wakaki M, Hamaguchi R, Kato R: A surgical case of quadruple lung cancer. Ann Thorac Cardiovasc Surg; 2010 Oct;16(5):345-50
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  • [Title] A surgical case of quadruple lung cancer.
  • Chest computed tomography (CT) showed a nodular shadow in the left S6 segment in April 2002, for which thoracoscopic partial resection of the lung was performed.
  • Because adenocarcinoma was diagnosed by intraoperative frozen sectioning, a left lower lobectomy and lymph node dissection were performed.
  • The pathological diagnosis was adenocarcinoma with mixed subtypes (AMS, pT1N0M0).
  • In March 2005, chest CT showed a nodular shadow in the right S3 segment, and thoracoscopic partial resection of the lung was performed.
  • Histologically, the middle-lobe tumor was solid adenocarcinoma with mucin (pT1N0M0).
  • Herein, we report a surgical case of quadruple lung cancer.
  • [MeSH-major] Adenocarcinoma / pathology. Adenocarcinoma / surgery. Lung Neoplasms / pathology. Lung Neoplasms / surgery

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  • (PMID = 21030922.001).
  • [ISSN] 2186-1005
  • [Journal-full-title] Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia
  • [ISO-abbreviation] Ann Thorac Cardiovasc Surg
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
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33. Sakao Y, Miyamoto H, Oh S, Takahashi N, Inagaki T, Miyasaka Y, Akaboshi T, Sakuraba M: The impact of cigarette smoking on prognosis in small adenocarcinomas of the lung: the association between histologic subtype and smoking status. J Thorac Oncol; 2008 Sep;3(9):958-62
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  • [Title] The impact of cigarette smoking on prognosis in small adenocarcinomas of the lung: the association between histologic subtype and smoking status.
  • OBJECTIVE: In this retrospective study, we clarified the impact of smoking on prognosis and the association of clinicopathological factors, particularly histologic subtype, in patients with small adenocarcinoma of the lung.
  • The clinicopathological records of the patients were examined for age, gender, nodal status (c-N and p-N), tumor size, serum carcinoembryonic antigen level, histologic subtype, and smoking history.
  • A histologic subtype was defined using a modified World Health Organization classification.
  • These subtypes are bronchioloalveolar carcinoma (BAC), adenocarcinoma with little or no BAC component (Non or min BAC), and mixed bronchioloalveolar carcinoma with other adenocarcinoma components.
  • Gender, serum carcinoembryonic antigen level, and histologic subtype were significantly associated with smoking status.
  • Histologic subtype (Non or min BAC) was the only significant prognostic factor in multivariate analyses.
  • The prevalence of smoking by histologic subtype was 27.3% for BAC, 43.2% for mixed bronchioloalveolar carcinoma, and 74.6% for Non or min BAC.
  • Furthermore, the smoking index (daily cigarette consumption times years of smoking) was significantly higher in Non or min BAC than in the other two subtypes.
  • In addition, patients with a high smoking index showed a greater percentage of Non or min BAC subtypes.
  • CONCLUSIONS: When adenocarcinomas were small (diameter </=2 cm) cigarette smoking and male gender were associated with Non or min BAC histologic subtypes, which are thought to have more aggressive biologic features resulting in poorer outcome compared with other subtypes.
  • [MeSH-major] Adenocarcinoma / pathology. Adenocarcinoma, Bronchiolo-Alveolar / pathology. Lung Neoplasms / pathology. Smoking / adverse effects

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  • (PMID = 18758296.001).
  • [ISSN] 1556-1380
  • [Journal-full-title] Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
  • [ISO-abbreviation] J Thorac Oncol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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34. Luu M, Sabo E, de la Monte SM, Greaves W, Wang J, Tavares R, Simao L, Wands JR, Resnick MB, Wang L: Prognostic value of aspartyl (asparaginyl)-beta-hydroxylase/humbug expression in non-small cell lung carcinoma. Hum Pathol; 2009 May;40(5):639-44
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  • [Title] Prognostic value of aspartyl (asparaginyl)-beta-hydroxylase/humbug expression in non-small cell lung carcinoma.
  • Despite improvements in the detection and use of biomarkers, including epidermal growth factor receptor, ERCC1, and p16, the 5-year survival rate with non-small cell lung cancer remains at 15%.
  • We now characterize the prognostic use of aspartyl (asparaginyl)-beta-hydroxylase/humbug immunoreactivity in different subtypes of non-small cell lung cancer.
  • Tissue microarrays including 375 paraffin-embedded non-small cell lung cancers (195 adenocarcinomas; 18 bronchioloalveolar carcinomas; 113 squamous cell carcinomas; and 49 large cell carcinomas) were immunostained with FB50 monoclonal antibody, which recognizes human aspartyl (asparaginyl)-beta-hydroxylase/humbug.
  • High levels of FB50 immunoreactivity were more often detected in adenocarcinomas (28% for adenocarcinoma, 17% for bronchioloalveolar carcinoma), compared with squamous cell carcinomas (10%) and large cell carcinomas (10%).
  • High levels of FB50 immunohistochemical staining correlate with poor prognosis in non-small cell lung cancer, particularly squamous cell carcinoma subtype.

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  • (PMID = 19200576.001).
  • [ISSN] 1532-8392
  • [Journal-full-title] Human pathology
  • [ISO-abbreviation] Hum. Pathol.
  • [Language] ENG
  • [Grant] United States / NIAAA NIH HHS / AA / AA011431-12A1; United States / NIAAA NIH HHS / AA / AA012908-04; United States / NIAAA NIH HHS / AA / R37 AA011431; United States / NIAAA NIH HHS / AA / AA016126-05; United States / NIAAA NIH HHS / AA / AA011431-12; United States / NIAAA NIH HHS / AA / K24 AA016126-04; United States / NCRR NIH HHS / RR / P20 RR024484-01; United States / NIAAA NIH HHS / AA / R01 AA012908-04; United States / NIAAA NIH HHS / AA / R01 AA012908-03; United States / NIAAA NIH HHS / AA / AA016126-04; United States / NIAAA NIH HHS / AA / R01 AA012908; United States / NIAAA NIH HHS / AA / R56 AA011431-12; United States / NIAAA NIH HHS / AA / R56 AA011431; United States / NIGMS NIH HHS / GM / P20 GM104937; United States / NIAAA NIH HHS / AA / R01 AA012908-08; United States / NCRR NIH HHS / RR / P20 RR024484; United States / NIAAA NIH HHS / AA / AA012908-08; United States / NIAAA NIH HHS / AA / K24 AA016126; United States / NIAAA NIH HHS / AA / R37 AA011431-12A1; United States / NIAAA NIH HHS / AA / AA012908-03; United States / NCRR NIH HHS / RR / RR024484-01; United States / NIAAA NIH HHS / AA / K24 AA016126-05
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Biomarkers, Tumor; EC 1.- / Mixed Function Oxygenases; EC 1.14.11.- / aspartic acid 2-oxoglutarate-dependent dioxygenase
  • [Other-IDs] NLM/ NIHMS208790; NLM/ PMC2893029
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35. Okada A, Shimmyo T, Hashimoto T, Kobayashi Y, Miyagi Y, Ishikawa Y, Nakagawa K, Hayashi J, Tsuchiya E: Predictive advantage of a cell type classification for pulmonary adenocarcinoma coupled with data for p53, K-ras and EGFR alterations. Cancer Sci; 2010 Jul;101(7):1745-53
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  • [Title] Predictive advantage of a cell type classification for pulmonary adenocarcinoma coupled with data for p53, K-ras and EGFR alterations.
  • We analyzed relationships between histological subtypes of pulmonary adenocarcinomas and three gene alterations (p53, K-ras, and epidermal growth factor receptor gene), or thyroid transcription factor-1 (TTF-1) expression, and also studied prognoses by the subtypes, with or without combined multiple gene mutation status.
  • A total of 223 consecutively resected pulmonary adenocarcinomas were sub-classified using either the World Health Organization (WHO) or our five-cell type (FCT) classification system (hobnail, columnar/cuboidal, mixed, polygonal/oval, and goblet cell types).
  • The most striking result was: while almost 70% of adenocarcinomas were sub-classified as a mixed subtype by WHO, the FCT classified many of them as other cell subtypes.
  • In contrast, subtypes of WHO did not show any association with the gene alteration or prognosis, and the FCT more suitably indicated sensitivity to gefitinib therapy than did WHO.
  • The FCT combined with multiple gene mutation status appears to be useful in indicating pathogenesis and predicting the biological nature of pulmonary adenocarcinomas, and it could facilitate development of new therapies for each subtype.
  • [MeSH-major] Adenocarcinoma / classification. Adenocarcinoma / genetics. Genes, p53. Genes, ras. Lung Neoplasms / classification. Lung Neoplasms / genetics. Receptor, Epidermal Growth Factor / genetics

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  • (PMID = 20491778.001).
  • [ISSN] 1349-7006
  • [Journal-full-title] Cancer science
  • [ISO-abbreviation] Cancer Sci.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Tumor Suppressor Protein p53; EC 2.7.10.1 / Receptor, Epidermal Growth Factor
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36. Righi L, Volante M, Rapa I, Scagliotti GV, Papotti M: Neuro-endocrine tumours of the lung. A review of relevant pathological and molecular data. Virchows Arch; 2007 Aug;451 Suppl 1:S51-9
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  • [Title] Neuro-endocrine tumours of the lung. A review of relevant pathological and molecular data.
  • Neuroendocrine (NE) tumours of the lung include pure and mixed forms.
  • In the mixed tumour group, the NE component is extensively represented in association with any of the non-small cell carcinoma subtypes (so-called combined carcinomas), or the NE component is restricted to a cell population scattered among adenocarcinoma cells (or more rarely within squamous or large cell carcinomas).
  • The molecular profile of NE tumours has been widely investigated to identify features helpful for the diagnosis, prognosis and even therapy for this special lung tumour category.
  • Specific chromosomal alterations, oncogene mutations and cell cycle molecule disregulation has been documented in NE tumours of the lung, as well as the expression of specific receptors or enzymes implicated in the response to biotherapies or to chemotherapeutic agents.
  • [MeSH-major] Lung Neoplasms / diagnosis. Neuroendocrine Tumors / diagnosis
  • [MeSH-minor] Diagnosis, Differential. Humans

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  • (PMID = 17684766.001).
  • [ISSN] 0945-6317
  • [Journal-full-title] Virchows Archiv : an international journal of pathology
  • [ISO-abbreviation] Virchows Arch.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Germany
  • [Number-of-references] 63
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37. Bastide K, Ugolin N, Levalois C, Bernaudin JF, Chevillard S: Are adenosquamous lung carcinomas a simple mix of adenocarcinomas and squamous cell carcinomas, or more complex at the molecular level? Lung Cancer; 2010 Apr;68(1):1-9
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  • [Title] Are adenosquamous lung carcinomas a simple mix of adenocarcinomas and squamous cell carcinomas, or more complex at the molecular level?
  • Adenocarcinomas (AC), squamous cell carcinomas (SCC) and adenosquamous carcinomas (ASC) are three histological subtypes of non-small-cell lung carcinomas (NSCLC).
  • ASC are morphologically mixed tumours that contain the two cell components AC and SCC.
  • Moreover, when classifying the three histological subtypes, using genes that discriminated AC and SCC, we observed that all ASC were classified as intermediate between the AC and SCC, some being closer to AC, others to SCC.
  • In conclusion, the ASC mixed lung tumours are more complex than simple mixes of AC and SCC components.
  • [MeSH-major] Adenocarcinoma / genetics. Carcinoma, Adenosquamous / genetics. Carcinoma, Squamous Cell / genetics. Lung / metabolism. Lung Neoplasms / genetics

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  • [Copyright] Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.
  • (PMID = 20004040.001).
  • [ISSN] 1872-8332
  • [Journal-full-title] Lung cancer (Amsterdam, Netherlands)
  • [ISO-abbreviation] Lung Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Ireland
  • [Chemical-registry-number] 0 / GATA6 Transcription Factor; 0 / Gata6 protein, rat; 0 / Mucin-1; 0 / Receptor, Notch2; Q74S4N8N1G / Radon
  • [Number-of-references] 61
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38. Koyama H, Ohno Y, Aoyama N, Onishi Y, Matsumoto K, Nogami M, Takenaka D, Nishio W, Ohbayashi C, Sugimura K: Comparison of STIR turbo SE imaging and diffusion-weighted imaging of the lung: capability for detection and subtype classification of pulmonary adenocarcinomas. Eur Radiol; 2010 Apr;20(4):790-800
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  • [Title] Comparison of STIR turbo SE imaging and diffusion-weighted imaging of the lung: capability for detection and subtype classification of pulmonary adenocarcinomas.
  • OBJECTIVE: The aim of the study was to evaluate the diagnostic performance of diffusion-weighted imaging (DWI) for detection and subtype classification in pulmonary adenocarcinomas through comparison with short TI inversion recovery turbo spin-echo imaging sequence (STIR).
  • The ADC values on DWI and the contrast ratio (CR) between cancer and muscle on STIR were measured and those were compared across subtype classifications.
  • Finally, ROC-based positive tests were performed to differentiate subtype classifications, and differentiation capabilities were compared.
  • The ADC values showed no significant difference regarding subtype classification; however, the CRs of bronchio-alveolar carcinomas (BACs) were significantly lower than those of other types (P < 0.05).
  • For differentiating adenocarcinomas with mixed subtypes from those with no BA component, there were no significant differences between the two sequences.
  • CONCLUSION: STIR is more sensitive for detection and subtype classification than DWI.
  • [MeSH-major] Adenocarcinoma / diagnosis. Algorithms. Diffusion Magnetic Resonance Imaging / methods. Image Interpretation, Computer-Assisted / methods. Lung / pathology. Lung Neoplasms / diagnosis

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  • (PMID = 19763578.001).
  • [ISSN] 1432-1084
  • [Journal-full-title] European radiology
  • [ISO-abbreviation] Eur Radiol
  • [Language] eng
  • [Publication-type] Comparative Study; Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
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39. Ishizuka T, Endo S, Tsubochi H, Nakano T, Miwa C, Watanabe K, Koyama S, Nokubi M, Sohara Y: [Mucinous bronchiolo-alveolar cell carcinoma with marked serum elevation of CA19-9: report of a case]. Kyobu Geka; 2009 Jun;62(6):509-12
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  • The pathologic study obtained by a transbronchial tumor biopsy revealed a mucinous adenocarcinoma The patient underwent video-assisted thoracoscopic right middle and lower bi-lobectomies with nodal sampling.
  • Postoperative course was uneventful Pathologic study revealed an adenocarcinoma with mixed subtypes, predominantly composed of mucinous bronchiolo-alveolar cell carcinoma (BAC).
  • Clinico-pathologic features of the lung cancer patients with serum elevation of CA19-9 and CA19-9 positivity in the cancer cells was discussed.
  • [MeSH-major] Adenocarcinoma, Bronchiolo-Alveolar / diagnosis. Biomarkers, Tumor / blood. CA-19-9 Antigen / blood. Lung Neoplasms / diagnosis

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  • (PMID = 19522216.001).
  • [ISSN] 0021-5252
  • [Journal-full-title] Kyobu geka. The Japanese journal of thoracic surgery
  • [ISO-abbreviation] Kyobu Geka
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / CA-19-9 Antigen
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40. Raz DJ, He B, Rosell R, Jablons DM: Bronchioloalveolar carcinoma: a review. Clin Lung Cancer; 2006 Mar;7(5):313-22
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  • Bronchioloalveolar carcinoma (BAC) is classified as a subset of lung adenocarcinoma but has a distinct clinical presentation, tumor biology, response to therapy, and prognosis compared with other subtypes of non-small-cell lung carcinoma (NSCLC).
  • Although pure BAC accounts for approximately 4% of lung cancers, tumors with histologically mixed BAC and adenocarcinoma account for > 20% of all NSCLCs, and the incidence of BAC might be increasing.
  • Bronchioloalveolar carcinoma histology is most commonly found in small lesions identified incidentally on chest radiographs or computed tomography scans and might represent a precursor lesion to invasive adenocarcinoma.
  • Patients with unresectable BAC are more likely to respond to the epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib than patients with other subtypes of NSCLC.
  • Stage for stage, patients with BAC have a higher rate of long-term survival but might have an increased rate of intrathoracic recurrence than patients with other subtypes of NSCLC.

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  • [CommentIn] Clin Lung Cancer. 2006 Mar;7(5):299 [16640799.001]
  • (PMID = 16640802.001).
  • [ISSN] 1525-7304
  • [Journal-full-title] Clinical lung cancer
  • [ISO-abbreviation] Clin Lung Cancer
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / CA093708-02; United States / NCI NIH HHS / CA / R01 CA093708; United States / NCI NIH HHS / CA / R01 CA093708-02
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 110
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41. Gandara DR, Aberle D, Lau D, Jett J, Akhurst T, Heelan R, Mulshine J, Berg C, Patz EF Jr: Radiographic imaging of bronchioloalveolar carcinoma: screening, patterns of presentation and response assessment. J Thorac Oncol; 2006 Nov;1(9 Suppl):S20-6
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  • Bronchioloalveolar carcinoma (BAC) is a previously uncommon subset of adenocarcinoma with unique epidemiology, pathology, radiographic presentation, clinical features, and natural history compared with other non-small cell lung cancer (NSCLC) subtypes.
  • However, in a subset of patients, rapid growth and death from bilateral diffuse consolidative disease occurs within months of diagnosis or recurrence.
  • The initial radiographic presentation of BAC varies considerably, from single ground glass opacities (GGOs) or nodules of mixed ground glass and solid attenuation to diffuse consolidative or bilateral multinodular disease.
  • The rising incidence of BAC is also reflected in recent lung cancer screening studies employing helical computed tomography (CT), where the differential diagnosis of GGOs includes not only BAC and overt adenocarcinoma, but inflammatory disease, focal fibrosis, and atypical adenomatous hyperplasia.
  • [MeSH-major] Adenocarcinoma, Bronchiolo-Alveolar / radiography. Carcinoma, Non-Small-Cell Lung / radiography. Lung Neoplasms / radiography. Neoplasm Recurrence, Local / radiography. Tomography, Spiral Computed
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Combined Modality Therapy. Diagnosis, Differential. Female. Follow-Up Studies. Humans. Male. Mass Screening / methods. Neoplasm Staging. Pneumonectomy / methods. Positron-Emission Tomography. Sensitivity and Specificity. Treatment Outcome

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  • [ErratumIn] J Thorac Oncol. 2007 Jan;2(1):11. Heelan, Robert [added]
  • (PMID = 17409997.001).
  • [ISSN] 1556-1380
  • [Journal-full-title] Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
  • [ISO-abbreviation] J Thorac Oncol
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
  • [Number-of-references] 65
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42. Levy BP, Drilon A, Makarian L, Patel AA, Grossbard ML: Systemic approaches for multifocal bronchioloalveolar carcinoma: is there an appropriate target? Oncology (Williston Park); 2010 Sep;24(10):888-98, 900
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  • Bronchioloalveolar carcinoma (BAC) is a subset of pulmonary adenocarcinoma characterized by distinct and unique pathological, molecular, radiographic, and clinical features.
  • While the incidence of pure BAC is rare, comprising only 1% to 4% of non-small-cell lung cancer (NSCLC), mixed subtypes (including BAC with focal invasion and adenocarcinoma with BAC features) represent as much as 20% of adenocarcinomas--and that figure may be increasing.
  • [MeSH-major] Adenocarcinoma, Bronchiolo-Alveolar / therapy. Lung Neoplasms / therapy

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  • [CommentIn] Oncology (Williston Park). 2010 Sep;24(10):900-1 [21138170.001]
  • [CommentIn] Oncology (Williston Park). 2010 Sep;24(10):907-8, 914 [21138171.001]
  • (PMID = 21138169.001).
  • [ISSN] 0890-9091
  • [Journal-full-title] Oncology (Williston Park, N.Y.)
  • [ISO-abbreviation] Oncology (Williston Park, N.Y.)
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] EC 2.7.10.1 / Receptor, Epidermal Growth Factor
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43. Shia J, Tang LH, Weiser MR, Brenner B, Adsay NV, Stelow EB, Saltz LB, Qin J, Landmann R, Leonard GD, Dhall D, Temple L, Guillem JG, Paty PB, Kelsen D, Wong WD, Klimstra DS: Is nonsmall cell type high-grade neuroendocrine carcinoma of the tubular gastrointestinal tract a distinct disease entity? Am J Surg Pathol; 2008 May;32(5):719-31
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  • In this study, we aimed at delineating the histologic and immunophenotypical spectrum of HGNECs of the GI tract with emphasis on histologic subtypes.
  • Guided primarily by the World Health Organization/International Association for the Study of Lung Cancer criteria for pulmonary neuroendocrine tumors, we were able to classify 87 high-grade GI tract tumors that initially carried a diagnosis of either poorly differentiated carcinoma with or without any neuroendocrine characteristics, small cell carcinoma, or combined adenocarcinoma-neuroendocrine carcinoma into the following 4 categories.
  • The third was mixed neuroendocrine carcinoma (n=11), which had intermediate histologic features (eg, cells with an increased nuclear/cytoplasmic ratio but with apparent nucleoli), and positive immunoreactivity for at least 1 neuroendocrine marker.
  • The fourth was poorly differentiated adenocarcinoma (n=17).
  • Further analysis showed that most HGNECs arising in the squamous lined parts (esophagus and anal canal) were small cell type (78%), whereas most involving the glandular mucosa were large cell (53%) or mixed (82%) type; associated adenocarcinomas were more frequent in large cell (61%) or mixed (36%) type than in small cell type (26%); and focal intracytoplasmic mucin was seen only in large cell or mixed type.
  • No significant survival difference was observed among the different histologic subtypes.
  • There are differences in certain pathologic features between small cell and nonsmall cell types, whereas the differences between the subtypes of nonsmall cell category (large cell versus mixed) are less distinct.
  • Given the current uncertainty as to whether large cell neuroendocrine carcinoma is as chemosensitive as small cell carcinoma even in the lung, our data provide further evidence in favor of a dichotomous classification scheme (small cell vs. nonsmall cell) for HGNEC of the GI tract.
  • Separation of nonsmall cell type into large cell and mixed subtypes may not be necessary.
  • [MeSH-major] Adenocarcinoma / diagnosis. Carcinoma, Neuroendocrine / diagnosis. Carcinoma, Small Cell / diagnosis. Gastrointestinal Neoplasms / diagnosis. Gastrointestinal Tract / pathology
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Biomarkers, Tumor / analysis. Diagnosis, Differential. Female. Humans. Male. Middle Aged. Neoplasms, Multiple Primary. New York / epidemiology. Survival Rate

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  • (PMID = 18360283.001).
  • [ISSN] 1532-0979
  • [Journal-full-title] The American journal of surgical pathology
  • [ISO-abbreviation] Am. J. Surg. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor
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44. Raspollini MR, Comin CE, Crisci A, Chilosi M: The use of placental S100 (S100P), GATA3 and napsin A in the differential diagnosis of primary adenocarcinoma of the bladder and bladder metastasis from adenocarcinoma of the lung. Pathologica; 2010 Feb;102(1):33-5
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  • [Title] The use of placental S100 (S100P), GATA3 and napsin A in the differential diagnosis of primary adenocarcinoma of the bladder and bladder metastasis from adenocarcinoma of the lung.
  • Primary bladder adenocarcinoma accounts for 0.5-2% of all malignant bladder tumours.
  • Herein, we describe an adenocarcinoma deeply infiltrating the bladder wall, with no morphologic features of transitional cell carcinoma, in a patient with a previous diagnosis of primary lung adenocarcinoma, mixed subtype.
  • In this case, the use of a limited immunohistochemical panel including napsin A, a recently described highly sensitive marker for lung adenocarcinoma, GATA3 and S100P, two novel markers of urothelial differentiation, was of crucial importance in differentiating between lung adenocarcinoma metastatic to the bladder and primary bladder adenocarcinoma.
  • [MeSH-major] Adenocarcinoma. Aspartic Acid Endopeptidases / metabolism. Biomarkers, Tumor / metabolism. GATA3 Transcription Factor / metabolism. Lung Neoplasms. S100 Proteins / metabolism. Urinary Bladder Neoplasms

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  • (PMID = 20731252.001).
  • [ISSN] 0031-2983
  • [Journal-full-title] Pathologica
  • [ISO-abbreviation] Pathologica
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / GATA3 Transcription Factor; 0 / GATA3 protein, human; 0 / S100 Proteins; EC 3.4.23.- / Aspartic Acid Endopeptidases; EC 3.4.23.- / NAPSA protein, human
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45. Zhang PJ, Gao HG, Pasha TL, Litzky L, Livolsi VA: TTF-1 expression in ovarian and uterine epithelial neoplasia and its potential significance, an immunohistochemical assessment with multiple monoclonal antibodies and different secondary detection systems. Int J Gynecol Pathol; 2009 Jan;28(1):10-8
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  • Thyroid transcription factor-1 (TTF-1) is a 38-kd homeodomain containing DNA-binding protein, identified in thyroid and lung as a regulator of thyroid-specific genes and surfactant and Clara cell secretory protein gene expression.
  • TTF-1 has been used as a reliable lineage marker for lung adenocarcinoma and thyroid carcinoma in surgical pathology.
  • By using SPT24/Refine/Bond Max, TTF-1 reactivity could be detected in all major histologic subtypes of gynecologic tumors and up to 26% of all cases tested on routine surgical specimens and 6.4% on TMA.
  • TTF-1 was most frequently detected in uterine malignant mixed Müllerian tumor (82%), more common in uterine tumors than ovarian tumors, and more common in surgical specimen than TMA.
  • TTF 1 immunostaining has the potential to misguide a pathologist to conclude an ovarian or endometrial tumor being a lung metastasis.

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  • (PMID = 19047914.001).
  • [ISSN] 1538-7151
  • [Journal-full-title] International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists
  • [ISO-abbreviation] Int. J. Gynecol. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Biomarkers, Tumor; 0 / Nuclear Proteins; 0 / Transcription Factors; 0 / thyroid nuclear factor 1
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46. Szczepulska-Wójcik E, Langfort R, Roszkowski-Sliz K: [A comparative evaluation of immunohistochemical markers for the differential diagnosis between malignant mesothelioma, non-small cell carcinoma involving the pleura, and benign reactive mesothelial cell proliferation]. Pneumonol Alergol Pol; 2007;75(1):57-69
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  • [Title] [A comparative evaluation of immunohistochemical markers for the differential diagnosis between malignant mesothelioma, non-small cell carcinoma involving the pleura, and benign reactive mesothelial cell proliferation].
  • INTRODUCTION: Histopathological diagnosis of malignant mesothelioma (MM) and differentiating it from tumors infiltrating the pleura is very difficult.
  • The objective of this study was to evaluate the significance of selected immunohistochemical stains in differentiating MM from non-small cell lung cancers infiltrating the pleura and from benign reactive mesothelial cell proliferation.
  • It included broad-spectrum antibodies to cytokeratins (CKAE1/AE3, CKMNF116), vimentin, epithelial membrane antigen (EMA), mesothelial cells (HBME1, CK5/6, calretinin), adenocarcinoma cells (BerEp4, B72.3, CEA, TTF1), antibodies enabling the assessment of proliferation (Mib1) and cell-cycle regulating proteins (p53).
  • Positive staining for HBME1, CK5/6, and calretinin was seen only in the epithelioid and mixed subtypes of MM; the respective percentages of positive reactions were: HBME1, 90.2% and 73.3%; CK5/6 58.2% and 53.3%; calretinin, 72% and 75%.
  • Non-small cell lung cancers infiltrating the pleura: Coexpression of cytokeratin and vimentin was found in 17.6% of the cases, positive staining of membranes for EMA, in 13% cases.
  • CONCLUSION: In diagnosing mesothelioma it is necessary to use a panel of immunohistochemical stains, which should contain antibodies to markers for adenocarcinoma and mesothelioma.
  • In the diagnosis of spindle-cell pleural tumors and the fibrous form of MM and benign reactive mesothelial cell proliferation , markers of mesothelial cells are noncontributory.
  • Immunohistochemical staining fails to identify a reactive process, but a diffuse, positive stain for EMA and the presence of protein p53 support the diagnosis of MM.
  • [MeSH-major] Antigens, Tumor-Associated, Carbohydrate / analysis. Biomarkers, Tumor / analysis. Carcinoma, Non-Small-Cell Lung / pathology. Mesothelioma / pathology. Neoplasm Proteins / analysis. Neoplasms, Mesothelial / pathology. Pleural Neoplasms / pathology
  • [MeSH-minor] Aged. Antibodies, Monoclonal / analysis. Diagnosis, Differential. Epithelium / chemistry. Epithelium / pathology. Female. Humans. Hyperplasia / pathology. Immunohistochemistry. Lung / chemistry. Lung / pathology. Male. Middle Aged. Pleura / chemistry. Pleura / pathology. Pleural Effusion / chemistry. Sensitivity and Specificity

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  • (PMID = 17541913.001).
  • [ISSN] 0867-7077
  • [Journal-full-title] Pneumonologia i alergologia polska
  • [ISO-abbreviation] Pneumonol Alergol Pol
  • [Language] pol
  • [Publication-type] Comparative Study; English Abstract; Evaluation Studies; Journal Article
  • [Publication-country] Poland
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antigens, Tumor-Associated, Carbohydrate; 0 / Biomarkers, Tumor; 0 / Neoplasm Proteins
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47. Zhang GY, Ahmed N, Riley C, Oliva K, Barker G, Quinn MA, Rice GE: Enhanced expression of peroxisome proliferator-activated receptor gamma in epithelial ovarian carcinoma. Br J Cancer; 2005 Jan 17;92(1):113-9
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  • Previous studies have demonstrated the expression of PPARgamma in several tumours including colon, breast, bladder, prostate, lung and stomach.
  • This study demonstrates the relative expression of PPARgamma in normal ovaries and different pathological grades of ovarian tumours of serous, mucinous, endometrioid, clear cell and mixed subtypes.
  • [MeSH-minor] Adenocarcinoma, Clear Cell / metabolism. Blotting, Western. Carcinoma, Endometrioid / metabolism. Cystadenocarcinoma, Mucinous / metabolism. Cystadenocarcinoma, Serous / metabolism. Female. Humans. Immunohistochemistry. Ovary / metabolism

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  • (PMID = 15583697.001).
  • [ISSN] 0007-0920
  • [Journal-full-title] British journal of cancer
  • [ISO-abbreviation] Br. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / PPAR gamma
  • [Other-IDs] NLM/ PMC2361744
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