MET overexpression, gene amplification and relevant clinicopathological features in gastric adenocarcinoma

Abstract

This study was conducted to investigate the expression of MET in Chinese gastric adenocarcinoma cohort, the correlation between MET overexpression and clinical pathological features, HER2 expression and MET gene amplification. A total of 816 gastric adenocarcinoma patients were included and MET and HER2 immunohistochemical (IHC) staining were performed. IHC and dual-color silver in situ hybridization analysis were performed in the tissue microarrays, constructed from the 240 patients who were randomly selected. MET overexpression (IHC 3+) was observed in 6.0% (49/816) of the cohort. MET overexpression rate was higher in patients with poor prognostic factors, such as clinical stages III/IV (p =0.012) and pathologic stages T3/T4 (p =0.027). The HER2 overexpression (IHC 3+) rate was 8.8% (72/816) and MET overexpression rate was higher in HER2 positive patients (9.7%, 7/72). A high concordance rate (94.6%) between MET overexpression and gene amplification was demonstrated. Therefore, MET overexpression could serve as a prognostic biomarker and a potential therapeutic target for gastric cancer.

Keywords: MET gene amplification; MET overexpression; biomarker; gastric cancer; immunohistochemistry.

Figure 1. Representative microphotographs (A-H, ×200) of gastric cancer H&E staining A. and MET expression scored as 1+ B. 2+ C. 3+ D. in the membrane

And MET expression interpreted as 0 E. 1+ F. 2+ G. and 3+ H. in both membrane and cytoplasm of tumor cells. Representative microphotographs of MET DISH (I-L, ×400): disomy of normal gastric musco (IHC -) I. IHC 1+ J. IHC 2+ K. and gene amplification L. cases by DISH are shown.

Figure 2. Representative microphotographs of MET overexpression heterogeneity are showed (A&B, ×200)

Positive IHC staining of MET was seen in the right area but negative or weak staining in the left area in both picture A. and B.