Genomic Profiling With Large-Scale Next-Generation Sequencing Panels Distinguishes Separate Primary Lung Adenocarcinomas From Intrapulmonary Metastases

Ching-Yeuh Yang, Yi-Chen Yeh, Lei-Chi Wang, Yen-Yu Lin, Shin-Ying Lin, Shu-Ying Wang, Ping-Yuan Chu, Zih-Yu Liu, Yu-Chi Su, Hsiang-Ling Ho, Teh-Ying Chou

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4 Citations (Scopus)

Abstract

The distinction between different separate primary lung cancers (SPLCs) and intrapulmonary metastases (IPMs) is a challenging but clinically significant issue. Histopathology-based classification is the current practice; however, it is subjective and affected by interobserver variability. Recently, next-generation sequencing (NGS) panels have been used in lung cancer diagnostics. This study aimed to investigate the value of large-scale NGS panels for distinguishing between SPLCs and IPMs. A total of 32 patients with 69 lung adenocarcinomas were included. Comprehensive histopathologic assessments of multiple pulmonary adenocarcinomas were performed independently by 3 pathologists. The consensus of histopathologic classification was determined by a majority vote. Genomic analysis was performed using an amplicon-based large-scale NGS panel, targeting single-nucleotide variants and short insertions and deletions in 409 genes. Tumor pairs were classified as SPLCs or IPMs according to a predefined molecular classification algorithm. Using NGS and our molecular classification algorithm, 97.6% of the tumor pairs can be unambiguously classified as SPLCs or IPMs. The molecular classification was predictive of postoperative clinical outcomes in terms of overall survival (P = .015) and recurrence-free interval (P = .0012). There was a moderate interobserver agreement regarding histopathologic classification (κ = 0.524 at the tumor pair level). The concordance between histopathologic and molecular classification was 100% in cases where pathologists reached a complete agreement but only 53.3% where they did not. This study showed that large-scale NGS panels are a powerful modality that can help distinguish SPLCs from IPMs in patients with multiple lung adenocarcinomas and objectively provide accurate risk stratification.

Original languageEnglish
Pages (from-to)100047
JournalModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
Volume36
Issue number3
DOIs
Publication statusE-pub ahead of print - Jan 2023

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