Comprehensive Next-Generation Sequencing Unambiguously Distinguishes Separate Primary Lung Carcinomas From Intrapulmonary Metastases: Comparison with Standard Histopathologic Approach.
Adenocarcinoma of Lung
/ genetics
Biomarkers, Tumor
/ genetics
Carcinoma, Large Cell
/ genetics
Carcinoma, Non-Small-Cell Lung
/ genetics
Carcinoma, Squamous Cell
/ genetics
Diagnosis, Differential
Genome, Human
High-Throughput Nucleotide Sequencing
/ methods
Humans
Lung Neoplasms
/ genetics
Prognosis
Prospective Studies
Survival Rate
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 12 2019
01 12 2019
Historique:
received:
28
05
2019
revised:
30
07
2019
accepted:
26
08
2019
pubmed:
1
9
2019
medline:
22
9
2020
entrez:
1
9
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 31471310
pii: 1078-0432.CCR-19-1700
doi: 10.1158/1078-0432.CCR-19-1700
pmc: PMC7713586
mid: NIHMS1640224
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7113-7125Subventions
Organisme : NCI NIH HHS
ID : P01 CA129243
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA217169
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
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