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

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,...

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Veröffentlicht in:Modern pathology 2023-03, Vol.36 (3), p.100047-100047, Article 100047
Hauptverfasser: Yang, Ching-Yeuh, Yeh, Yi-Chen, Wang, Lei-Chi, Lin, Yen-Yu, Lin, Shin-Ying, Wang, Shu-Ying, Chu, Ping-Yuan, Liu, Zih-Yu, Su, Yu-Chi, Ho, Hsiang-Ling, Chou, Teh-Ying
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container_issue 3
container_start_page 100047
container_title Modern pathology
container_volume 36
creator Yang, Ching-Yeuh
Yeh, Yi-Chen
Wang, Lei-Chi
Lin, Yen-Yu
Lin, Shin-Ying
Wang, Shu-Ying
Chu, Ping-Yuan
Liu, Zih-Yu
Su, Yu-Chi
Ho, Hsiang-Ling
Chou, Teh-Ying
description 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.
doi_str_mv 10.1016/j.modpat.2022.100047
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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. 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Yeh, Yi-Chen ; Wang, Lei-Chi ; Lin, Yen-Yu ; Lin, Shin-Ying ; Wang, Shu-Ying ; Chu, Ping-Yuan ; Liu, Zih-Yu ; Su, Yu-Chi ; Ho, Hsiang-Ling ; Chou, Teh-Ying</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-7f5d359102e682cbc62a02f72b47fd1831e141813a3d9ee0a6293d723545414a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>adenocarcinoma</topic><topic>Adenocarcinoma of Lung - genetics</topic><topic>Genomics</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Humans</topic><topic>Lung Neoplasms - diagnosis</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>metastasis</topic><topic>next-generation sequencing</topic><topic>pathology</topic><topic>prognosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Ching-Yeuh</creatorcontrib><creatorcontrib>Yeh, Yi-Chen</creatorcontrib><creatorcontrib>Wang, Lei-Chi</creatorcontrib><creatorcontrib>Lin, Yen-Yu</creatorcontrib><creatorcontrib>Lin, Shin-Ying</creatorcontrib><creatorcontrib>Wang, Shu-Ying</creatorcontrib><creatorcontrib>Chu, Ping-Yuan</creatorcontrib><creatorcontrib>Liu, Zih-Yu</creatorcontrib><creatorcontrib>Su, Yu-Chi</creatorcontrib><creatorcontrib>Ho, Hsiang-Ling</creatorcontrib><creatorcontrib>Chou, Teh-Ying</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Modern pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Ching-Yeuh</au><au>Yeh, Yi-Chen</au><au>Wang, Lei-Chi</au><au>Lin, Yen-Yu</au><au>Lin, Shin-Ying</au><au>Wang, Shu-Ying</au><au>Chu, Ping-Yuan</au><au>Liu, Zih-Yu</au><au>Su, Yu-Chi</au><au>Ho, Hsiang-Ling</au><au>Chou, Teh-Ying</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genomic Profiling With Large-Scale Next-Generation Sequencing Panels Distinguishes Separate Primary Lung Adenocarcinomas From Intrapulmonary Metastases</atitle><jtitle>Modern pathology</jtitle><addtitle>Mod Pathol</addtitle><date>2023-03</date><risdate>2023</risdate><volume>36</volume><issue>3</issue><spage>100047</spage><epage>100047</epage><pages>100047-100047</pages><artnum>100047</artnum><issn>0893-3952</issn><eissn>1530-0285</eissn><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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>36788096</pmid><doi>10.1016/j.modpat.2022.100047</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-2855-5756</orcidid><orcidid>https://orcid.org/0000-0001-5844-477X</orcidid></addata></record>
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subjects adenocarcinoma
Adenocarcinoma of Lung - genetics
Genomics
High-Throughput Nucleotide Sequencing
Humans
Lung Neoplasms - diagnosis
Lung Neoplasms - genetics
Lung Neoplasms - pathology
metastasis
next-generation sequencing
pathology
prognosis
title Genomic Profiling With Large-Scale Next-Generation Sequencing Panels Distinguishes Separate Primary Lung Adenocarcinomas From Intrapulmonary Metastases
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