The Features Of C-MET Genetic Abnormality In Lung Adenocarcinoma And The Relativity With EGFR

Objective To discuss the clinical and pathological features of MET(Mesenchymal-epithelial transition factor) overexpression which caused by c-METgenetic abnormality in human lung adenocarcinoma tissues; What kind of GCN (genecopy number) abnormality made MET highly and persistently phosphorylated；Thecorrelation analysis between c-MET and EGFR (Epidermal growth factor receptor)mutation；To investigate whether there are any differences of c-MET and EGFRmutation in lung, pleura or lymph node.Method100lung adenocarcinoma tissues from chemotherapy and molecular targetedtherapy-naive patients are collected for the experiments：1. The expression of c-MET and the phosphorylation level (Tyr1234,Tyr1235) inall the100tissues were detected with Immunohistochemistry;2. The tissue microarrays (TMA) with75cases which were chosen from thecohort above were built, then tissue chips were made. c-MET GCN detection wasproceeded on the tissue chips with FISH(Fluorescent in situ hybridization) technique;3. The29kinds of EGFR mutation were respectively examined in the100caseswith RTFQ PCR(Realtime fluores-cence quantitative PCR) technique．Results1.The expression and activation level of c-MET:(1)The constituent ratio ofc-MET positive expression in lung adenocarcinoma is43.0%(43/100); The ratio isrelated with smoking (P＜0.05)，the MET expression rate in smoking cohort (28.2%)was obviously lower than the one without smoking (52.5%), the correlations withage,sex,pathological stage and tissue types were not found．(2)The constituent ratio ofp-MET(MET phosphorylation) positive is2.0%(2/100); No correlation was foundbetween p-MET and various statistical features.(3)2cases of the MET positive cohortwere highly phosphorylated (2/43).2.c-MET GCN detection results (75cases were detected, failure of4,the diagnoses were confirmed in71cases):(1)The constituent ratio of c-MET GCNabnormality is14.1%(10/71), the ratio is related with M stage (P＜0.05), M1cohorthas a higher detection rate than M0; the correlations with other features were notfound(P＞0.05).(2)The constituent ratio of c-MET high polysomy is11.3%(8/71)and a similar feature was found like GCN abnormality.(3)Only the2highlyphosphorylated cases were detected with c-MET amplification, the constituent ratio is2.8%(2/71); No correlation was found between c-MET amplification and variousstatistical features.3.EGFR mutation detection results: EGFR mutation constituent ratio is52%(52/100)，3of them is T790M. The ratio is related with histologic position (P＜0.05)，The mutation constituent ratio of lung adenocarcinoma is higher in pleura(84.6%)than lung(51.1%) or lymph node(21.4%).4.After correlation analysis no correlation was found in the detection resultsbetween EGFR and MET.Conclusion1.The expression of c-MET is frequently seen in lung adenocarcinoma patientswith out smoking, only4.7%of the MET positive cohort were highlyphosphorylated．2. c-MET amplification is the key reason that made MET highly andpersistently phosphorylated；c-MET GCN abnormality may enhance the ability ofmetastasis in lung adenocarcinoma, which lead to the acquired resistance toEGFR-TKI (Epidermal growth factor receptor-tyrosine kinases inhibitor)； Thedetection is of great significance to assess the ability of metastasis, prognosis and thetherapeutic efficacy of MET-TKI in lung adenocarcinoma.3. No correlation was found between EGFR mutation and the detection resultsof MET；The detection rate of EGFR mutation is higher in pleura than lung or lymphnode, promptting EGFR may be the factor that enhance the invasion ability in lungadenocarcinoma.