Comprehensive Next-Generation Sequencing Unambiguously Distinguishes Separate Primary Lung Carcinomas From Intrapulmonary Metastases: Comparison with Standard Histopathologic Approach

肺癌 医学 腺癌 体细胞 肿瘤科 原发性肿瘤 前瞻性队列研究 病理 癌症 内科学 生物 转移 基因 遗传学
作者
Jason C. Chang,Deepu Alex,Matthew Bott,Kay See Tan,Venkatraman Seshan,Andrew Golden,Jennifer L. Sauter,Darren J. Buonocore,Chad Vanderbilt,Sounak Gupta,Patrice Desmeules,Francis M. Bodd,Gregory J. Riely,Valerie W. Rusch,David R. Jones,Maria E. Arcila,William D. Travis,Marc Ladanyi,Natasha Rekhtman
出处
期刊:Clinical Cancer Research [American Association for Cancer Research]
卷期号:25 (23): 7113-7125 被引量:52
标识
DOI:10.1158/1078-0432.ccr-19-1700
摘要

Abstract Purpose: In patients with >1 non–small cell lung carcinoma (NSCLC), the distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is a common diagnostic dilemma with critical staging implications. Here, we compared the performance of comprehensive next-generation sequencing (NGS) with standard histopathologic approaches for distinguishing NSCLC clonal relationships in clinical practice. Experimental Design: We queried 4,119 NSCLCs analyzed by 341–468 gene MSK-IMPACT NGS assay for patients with >1 surgically resected tumor profiled by NGS. Tumor relatedness predicted by prospective histopathologic assessment was contrasted with comparative genomic profiling by subsequent NGS. Results: Sixty patients with NGS performed on >1 NSCLCs were identified, yielding 76 tumor pairs. NGS classified tumor pairs into 51 definite SPLCs (median, 14; up to 72 unique somatic mutations per pair), and 25 IPMs (24 definite, one high probability; median, 5; up to 16 shared somatic mutations per pair). Prospective histologic prediction was discordant with NGS in 17 cases (22%), particularly in the prediction of IPMs (44% discordant). Retrospective review highlighted several histologic challenges, including morphologic progression in some IPMs. We subsampled MSK-IMPACT data to model the performance of less comprehensive assays, and identified several clinicopathologic differences between NGS-defined tumor pairs, including increased risk of subsequent recurrence for IPMs. Conclusions: Comprehensive NGS allows unambiguous delineation of clonal relationship among NSCLCs. In comparison, standard histopathologic approach is adequate in most cases, but has notable limitations in the recognition of IPMs. Our results support the adoption of broad panel NGS to supplement histology for robust discrimination of NSCLC clonal relationships in clinical practice.
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