High Discrepancy of Driver Mutations in Patients with NSCLC and Synchronous Multiple Lung Ground-Glass Nodules

Wu, Chunyan; Zhao, Chao; Yang, Yang; He, Yayi; Hou, Likun; Li, Xuefei; Gao, Guanghui; Shi, Jingyun; Ren, Shengxiang; Chu, Haiqing; Zhou, Caicun; Zhang, Jun; Schmid-Bindert, Gerald

doi:10.1097/jto.0000000000000487

Cited by 128 publications

(120 citation statements)

References 39 publications

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“…While, different observations were found last year (19,20). One of the studies enrolled 35 patients with 72 lesions.…”

Section: Discussionmentioning

confidence: 99%

“…One of the studies enrolled 35 patients with 72 lesions. Among them, 33 (45.8%) tumor lesions were found harboring EGFR mutations, and their founding indicated that there was a high discrepancy of driver mutations in NSCLC patients with ground-glass nodules (GGNs) (19). Another research showed that EGFR mutation especially L858R was detected more frequently in invasive solid pattern and significantly less in pure GGO pattern in stage I lung adenocarcinoma (21).…”

Section: Discussionmentioning

confidence: 99%

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Correlation in histological subtypes with high resolution computed tomography signatures of early stage lung adenocarcinoma

Miao¹,

Zhang²,

Zou³

et al. 2017

Transl. Lung Cancer Res.

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“…While, different observations were found last year (19,20). One of the studies enrolled 35 patients with 72 lesions.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Correlation in histological subtypes with high resolution computed tomography signatures of early stage lung adenocarcinoma

Miao¹,

Zhang²,

Zou³

et al. 2017

Transl. Lung Cancer Res.

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“…This is similar to the previously published studies regardless of methodological approaches. 2,6,7,10,[23][24][25] The presence of discordant mutations most likely can be used as an indicator of a different clone. Earlier studies indicated a broad range of discordance (25-49%) in driver mutations (EGFR, KRAS) between primary and metastatic lung tumors that in part can be explained by different methodological approaches, although authors mostly suggested intratumoral heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

“…It is striking that many studies, including ours, failed to demonstrate correlation between clonality defined by genotype and outcomes. 9,10 Therefore, it is uncertain whether different mutations identify separate primary cancers or just a different clone within single tumor. Large prospective studies with precisely defined treatment management could potentially provide the answer.…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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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Clinicopathologic characteristics and outcomes of Chinese patients with non‐small‐cell lung cancer and BRAF mutation

et al. 2017

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BRAF mutation is one of the important driver oncogene in non‐small‐cell lung cancer (NSCLC). Data on Chinese patients with BRAF‐mutant NSCLC are inadequate. Hence, we conducted this study to investigate the clinicopathologic features and outcomes of Chinese patients with NSCLC and BRAF mutations. We identified patients with BRAF‐mutant NSCLC between January 2012 and April 2016. Patient characteristics and treatment outcomes were analyzed. In total, 1680 patients were included. Twenty‐eight (1.7%) patients harbored BRAF mutations. Compared to patients with non‐BRAF mutation, patients with BRAF mutations were associated with adenocarcinomas (89.3% vs. 70.6%, P = 0.048) and never smokers (78.6% vs. 56.7%, P = 0.019). There were no significant differences in the age, gender distribution, metastasis, or stage at first diagnosis between two groups. Response rates and progression‐free survival (PFS) were similar between patient with BRAF mutations and EGFR (5.6 vs. 5.8 months; P = 0.277) or KRAS (5.6 vs. 4.7 months; P = 0.741) mutations to first‐line chemotherapy. Compared to patients with non‐V600E mutations, patients with V600E‐mutated tumors had a shorter PFS to first‐line chemotherapy, although this did not reach statistical significance (5.2 vs. 6.4 months; P = 0.561). In multivariate analyses, only ECOG PS remained the independent predictor of overall survival (HR = 0.208; P = 0.004). In conclusion, BRAF mutation in Chinese patients with NSCLC was rare. BRAF mutation is more likely to be associated with adenocarcinoma and never smokers. BRAF mutations are not associated with enhanced chemosensitivity and novel and effective drugs inhibiting the BRAF pathway are in urgent need.

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High Discrepancy of Driver Mutations in Patients with NSCLC and Synchronous Multiple Lung Ground-Glass Nodules

Abstract: We found a high discrepancy of driver mutations among NSCLC patients with GGNs and a favorable prognosis after multiple lesions resection, which support surgical resection in this situation as a reasonable approach.

Cited by 128 publications

References 39 publications

Correlation in histological subtypes with high resolution computed tomography signatures of early stage lung adenocarcinoma

Correlation in histological subtypes with high resolution computed tomography signatures of early stage lung adenocarcinoma

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

Clinicopathologic characteristics and outcomes of Chinese patients with non‐small‐cell lung cancer and BRAF mutation

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