MET IHC Is a Poor Screen for MET Amplification or MET Exon 14 Mutations in Lung Adenocarcinomas: Data from a Tri-Institutional Cohort of the Lung Cancer Mutation Consortium.
FISH
Immunohistochemistry
Lung cancer
MET exon 14
MET-amplified
Next-generation sequencing
Journal
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
ISSN: 1556-1380
Titre abrégé: J Thorac Oncol
Pays: United States
ID NLM: 101274235
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
26
04
2019
revised:
04
06
2019
accepted:
07
06
2019
pubmed:
23
6
2019
medline:
18
8
2020
entrez:
23
6
2019
Statut:
ppublish
Résumé
MNNG HOS Transforming gene (MET) amplification and MET exon 14 (METex14) alterations in lung cancers affect sensitivity to MET proto-oncogene, receptor tyrosine kinase (MET [also known by the alias hepatocyte growth factor receptor]) inhibitors. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and immunohistochemistry (IHC) have been used to evaluate MET dependency. Here, we have determined the association of MET IHC with METex14 mutations and MET amplification. We collected data on a tri-institutional cohort from the Lung Cancer Mutation Consortium. All patients had metastatic lung adenocarcinomas and no prior targeted therapies. MET IHC positivity was defined by an H-score of 200 or higher using SP44 antibody. MET amplification was defined by copy number fold change of 1.8x or more with use of NGS or a MET-to-centromere of chromosome 7 ratio greater than 2.2 with use of FISH. We tested tissue from 181 patients for MET IHC, MET amplification, and METex14 mutations. Overall, 71 of 181 patients (39%) were MET IHC-positive, three of 181 (2%) were MET-amplified, and two of 181 (1%) harbored METex14 mutations. Of the MET-amplified cases, two were FISH positive with MET-to-centromere of chromosome 7 ratios of 3.1 and 3.3, one case was NGS positive with a fold change of 4.4x, and one of the three cases was MET IHC-positive. Of the 71 IHC-positive cases, one (1%) was MET-amplified and two (3%) were METex14-mutated. Of the MET IHC-negative cases, two of 110 (2%) were MET-amplified. In this study, nearly all MET IHC-positive cases were negative for MET amplification or METex14 mutations. MET IHC can also miss patients with MET amplification. The limited number of MET-amplified cases in this cohort makes it challenging to demonstrate an association between MET IHC and MET amplification. Nevertheless, IHC appears to be an inefficient screen for these genomic changes. MET amplification or METex14 mutations can best be detected by FISH and a multiplex NGS panel.
Identifiants
pubmed: 31228623
pii: S1556-0864(19)30474-5
doi: 10.1016/j.jtho.2019.06.009
pmc: PMC6708730
mid: NIHMS1535871
pii:
doi:
Substances chimiques
MAS1 protein, human
0
Proto-Oncogene Mas
0
MET protein, human
EC 2.7.10.1
Proto-Oncogene Proteins c-met
EC 2.7.10.1
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1666-1671Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R25 CA020449
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009207
Pays : United States
Informations de copyright
Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
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