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MET amplification, protein expression, and mutations in pulmonary adenocarcinoma

Cited 31 time in Web of Science Cited 31 time in Scopus
Authors
Park, Seongyeol; Koh, Jaemoon; Kim, Dong-Wan; Kim, Miso; Keam, Bhumsuk; Kim, Tae Min; Jeon, Yoon Kyung; Chung, Doo Hyun; Heo, Dae Seog
Issue Date
2015-12
Citation
Lung Cancer, Vol.90 No.3, pp.381-387
Keywords
METGene amplificationGene expressionMutationNon-small-cell lung carcinomaAdenocarcinoma
Abstract
Objectives: MET amplification, protein expression, and splice mutations at exon 14 are known to cause dysregulation of the MET/HGF pathway. Our study aimed to confirm the relationship among MET amplification, protein expression, and mutations in pulmonary adenocarcinoma. Materials and methods: MET protein expression by immunohistochemistry (IHC) and MET amplification by fluorescence in situ hybridization (FISH) were evaluated in 316 surgically resected lung adenocarcinomas. Patients were divided into 4 groups (IHC-negative/FISH-negative, IHC-negative/FISH-positive, IHC-positive/FISH-negative, and IHC-positive/FISH-positive), and 15-20 tumors in each group were randomly selected for mutation analyses to find splice mutations at exon 14. Results: An IHC score of 0-3 was found in 168 (53.2%), 71 (22.5%), 59 (18.7%), and 18 (5.7%) tumors, respectively. The mean gene copy number (GCN) was 3.56; MET FISH positivity was detected in 123 (38.9%) samples, and 26 (8.2%) of them were gene amplifications. MET amplification were significantly associated with the IHC score (P< 0.001, chi(2) test). Splice mutations were identified in only 2 (2.9%) of 70 cases. One had a MET IHC score of 2 and negative FISH without amplification; The other had a MET IHC score of 0 and positive FISH without amplification. MET IHC or FISH results were not prognostic indicators of overall survival in multivariate analysis. Conclusion: There is a significant relationship between MET amplification and protein expression, and selection of tumors with amplification using IHC was effective. However, because of its rarity, a selection strategy for mutated tumors is implausible using IHC or FISH. (c) 2015 Elsevier Ireland Ltd. All rights reserved.
ISSN
0169-5002
URI
http://hdl.handle.net/10371/165352
DOI
https://doi.org/10.1016/j.lungcan.2015.10.022
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College of Medicine/School of Medicine (의과대학/대학원)Cancer Research Institute (암연구소)Journal Papers (저널논문_암연구소)
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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