MET amplification, protein expression, and mutations in pulmonary adenocarcinoma

Abstract

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. 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. 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, χ(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. 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.