Clonality status of multifocal lung adenocarcinomas based on the mutation patterns of EGFR and K-ras

Takamochi, Kazuya; Oh, Shiaki; Matsuoka, Joe; Suzuki, Kenji

doi:10.1016/j.lungcan.2011.08.007

Cited by 63 publications

(48 citation statements)

References 29 publications

(33 reference statements)

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“…Secondary tumors in lung cancer patients are relatively frequent and a clonality analysis was performed in a relatively small patient cohort. Molecular analysis indicated that 20% of EGFR wild type tumors were followed by a KRAS mutant secondary tumor and 15% of EGFR mutant tumors were followed by a KRAS mutant secondary tumor, indicating the emergence of a molecularly distinct clone in these patients [15]. There are no novel data at hand concerning the clonality fidelity of progressing lung adenocarcinoma: previous reports suggested a 20% alteration rate at metastatic sites [16].…”

Section: Heterogeneity By Histology By Geneticsmentioning

confidence: 93%

The clinical relevance of KRAS gene mutation in non-small-cell lung cancer

Tı́már¹

2014

Current Opinion in Oncology

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Section: Heterogeneity By Histology By Geneticsmentioning

confidence: 93%

The clinical relevance of KRAS gene mutation in non-small-cell lung cancer

Tı́már¹

2014

Current Opinion in Oncology

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“…27,[48][49][50] Clonality studies comparing these multiple lesions in a single patient are limited and conflicting. Recent studies suggest that most of these are separate primary cancers; in those patients with multifocal GG/L lung cancer in which clonality could be assessed 71-83% were discordant, [51][52][53] However, earlier smaller studies suggested either the same 54,55 or separate lineage 56 for all lesions.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

The IASLC Lung Cancer Staging Project: Background Data and Proposals for the Application of TNM Staging Rules to Lung Cancer Presenting as Multiple Nodules with Ground Glass or Lepidic Features or a Pneumonic Type of Involvement in the Forthcoming Eighth Edition of the TNM Classification

Detterbeck

Marom

Arenberg

et al. 2016

Journal of Thoracic Oncology

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164

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For multifocal ground glass/lepidic tumors, we propose that the T category be determined by the highest T lesion, with either the number of tumors or m in parentheses to denote the multifocal nature, and that a single N and M category be used for all the lesions collectively-for example, T1a(3)N0M0 or T1b(m)N0M0. For diffuse pneumonic-type lung cancer we propose that the T category be designated by size (or T3) if in one lobe, as T4 if involving an ipsilateral different lobe, or as M1a if contralateral and that a single N and M category be used for all pulmonary areas of involvement.

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“…2,[4][5][6][7][8][9][10] The data from published reports indicate a highly variable percentage of multifocal tumors identified as clonally related (up to 70%) and all reports agree that multifocal tumors may arise either as metastases from a single tumor or as independent tumors. Discrepancy between clinical and molecular classification of originally presumed cases of multiple primary lung cancers ranged in different series from 18 to 30%.…”

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confidence: 92%

Morphological and molecular approach to synchronous non-small cell lung carcinomas: impact on staging

et al. 2016

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Distinction between multiple primary cancers and intrapulmonary metastases in patients with synchronous multifocal lung cancer can be challenging. Histological and genotypic assessment of multifocal lung tumors have been suggested to influence the staging. The aim of this study was to determine the role of morphology and genotype in staging of surgically treated multifocal non-small cell lung carcinoma. Synchronous lung cancers from 60 patients (42 with adenocarcinoma and 18 with squamous cell carcinoma), clinically considered to represent intrapulmonary metastases, were histologically subtyped according to the 2015 World Health Organization classification of lung tumors and subjected to genotypic analysis (KRAS, EGFR, BRAF, PIK3CA, ALK, MET and ROS1 in adenocarcinoma and PIK3CA and p16 in squamous cell carcinoma). Concordance between clinical criteria and histological subtyping was identified in about 50% of cases (Po 0.0001). Genotypically, 44% of adenocarcinomas and 60% of squamous cell carcinomas with identified molecular alterations were considered to be intrapulmonary metastases. Concordance between histological and molecular staging was observed in 89% of adenocarcinomas and 56% of squamous cell carcinomas. Univariate survival analyses failed to demonstrate significant differences in overall or cancer-specific survival in patients with adenocarcinoma and squamous cell carcinomas restaged according to histology and/or molecular profile. Lymph node metastases (N1/N2 vs N0) (P = 0.03) and age 465 years (P = 0.05) were associated with shorter overall survival. In addition, squamous cell carcinomas with p16 deletion showed shorter overall survival when compared with squamous cell carcinomas without p16 deletion (P = 0.05). No correlation between other molecular alterations, clinico-pathological characteristics and prognosis was found. Our study demonstrates that a comprehensive genotypic and morphological assessment of surgically treated multifocal lung cancers is feasible but not sufficient to establish their clonal relationship and prognosis. Modern Pathology (2016) 29, 735-742; doi:10.1038/modpathol.2016 published online 15 April 2016 The reported incidence of multiple synchronous tumors of the lung in recent series is up to 20%. 1,2 Staging of such tumors as independent primary tumors or intrapulmonary metastases is often challenging. Morphological criteria, especially those proposed by Martini and Melamed, 3 have been used as the main tool with the idea that morphology of metastases should match the primary tumor, while different morphology supports classification of tumors as unrelated separate primaries. However, clinico-pathological distinction between the two possibilities is not always possible and may not be prognostic.Over the past decade, multiple studies using different molecular approaches to analysis of synchronous lung tumor nodules have emerged, including DNA microsatellite analysis, CGH/aCHG and most recently next-generation sequencing. 2,[4][5][6][7][8][9][10] The data from published rep...

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Clonality status of multifocal lung adenocarcinomas based on the mutation patterns of EGFR and K-ras

Cited by 63 publications

References 29 publications

The clinical relevance of KRAS gene mutation in non-small-cell lung cancer

The clinical relevance of KRAS gene mutation in non-small-cell lung cancer

The IASLC Lung Cancer Staging Project: Background Data and Proposals for the Application of TNM Staging Rules to Lung Cancer Presenting as Multiple Nodules with Ground Glass or Lepidic Features or a Pneumonic Type of Involvement in the Forthcoming Eighth Edition of the TNM Classification

Morphological and molecular approach to synchronous non-small cell lung carcinomas: impact on staging

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