MET Expression And Gene Amplification In Advanced Lung Adenocarcinoma

Purpose:MET is the promotor of tumor pathogenesis and progression.Numerous MET inhibitors have been developed and are now being tested in clinical trials, especially in advanced non-small-cell lung cancer(NSCLC).The patient selection was based on immunohistochemistry (IHC) and/or gene copy number assessment.Therefore,it is important to understand the distribution and stratification of MET expression and gene amplification in lung adenocarcinoma.Methods:This study included98patients diagnosed of locally advanced or metastatic lung adenocarcinoma.The TNM stages range from Ⅲ-Ⅳ.Collect the patients’ histories and records.Detect the MET expression by immunohistochemistry and calculate the IHC score (0～300)。The cut off value was set at the median IHC score,or as the scoring system recommended in the Phase II MetMab clinical trial(≥50%of cells with2+or3+staining).MET gene copy number was assessed by fluorescence in situ hybridization(FISH,n=89patients).One of the positive criteria was the high gene copy number recommended by Cappuzzo in2009.The other one was a modefied UCCC criteria.Results:Median Met IHC score was193(range:0-300,n=98). According to MetMab criteria,IHC positivity rate was70%.No significant assciations were find to the clinical or pathological characteristic,or to the EGFR gene mutation and overall survival. In89tumors evaluable for MET copy number,6(6.7%) had tumors with an average of5or more copies nucleus.14patients were gene amplification positive according to the modefied UCCC criteria that we came up with,and with significant asscoiation with EGFR TKI no response and poor prognosis (P=0.001).Correlation between MET copy number and protein expression was significantly related(Pearson’s=0.210, p=0.048).Conclusion:The median IHC score may not be stable enough to be used in clinical trials.MetMab criteria can get a high positive rate, however with less specificity.Cappuzzo criteria in this experiment get very low positive patients,while the modified UCCC criteria may be an appropriate tool in defining MET FISH positive patients in advanced lung adenocarcinoma.