S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Clinical Medical Sciences (임상의과학과) Theses (Master's Degree_임상의과학과)
MET amplification, protein expression, and mutations in pulmonary adenocarcinoma
면역조직화학염색을 이용한 MET조절장애 폐선암 환자의 선별
- 의과대학 임상의과학과
- Issue Date
- 서울대학교 대학원
- MET ; Gene Amplification ; Gene Expression ; Mutation ; Non-Small-Cell Lung Carcinoma ; Adenocarcinoma
- 학위논문 (석사)-- 서울대학교 대학원 : 임상의과학과 전공, 2016. 2. 김동완.
- Introduction: The proper target of a MET inhibitor has not been demonstrated in lung cancer. MET amplification, protein expression, and splice mutations at exon 14 are known to cause dysregulation of the MET/HGF pathway. Our study aimed to establish the strategy for finding target population of MET inhibitor by confirming the relationship among MET amplification, protein expression, and mutations in pulmonary adenocarcinoma.
Methods: MET protein expression by immunohistochemistry (IHC) and MET amplification by fluorescence in situ hybridization (FISH) were evaluated in 316 surgically resected lung adenocarcinomas. The IHC score was defined by the modified criteria used in the clinical trial for the MET inhibitor, and the score of 2 or 3 was defined as positivity. MET gene copy number (GCN) and amplification was defined by University of Coloradeo Cancer Center criteria. 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, 1, 2, and 3 was found in 168 (53.2%), 71 (22.5%), 59 (18.7%), and 18 (5.7%) tumors, respectively. The mean GCN was 3.56 (standard deviation 1.5)
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, χ2 test), and the positive predictive value of the IHC score of 3 for predicting amplification was 44.4%. 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.
Conclusions: 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.