MET is overexpressed in microsatellite instability-high gastric carcinoma

Abstract

Background: MET is a tyrosine kinase receptor for the hepatocyte growth factor, and its overexpression is a poor prognostic factor in gastric carcinomas. Programmed death-ligand 1 (PD-L1) is an important biomarker of immunotherapy and is frequently positive in microsatellite instability-high (MSI-H) gastric carcinomas. In lung cancers, MET activation up-regulates PD-L1 expression. In this study, we investigated expression of MET and PD-L1 in MSI-H gastric carcinoma and the effects on prognosis.

Methods: MET and PD-L1 (SP142) immunohistochemistry was performed in 73 gastric carcinomas with MSI-H. In cases with MET overexpression, we performed fluorescent in situ hybridization (FISH). PD-L1 expression was calculated from both tumor cells (2+ and 3+ in > 10% of tumor cells was defined as PD-L1^TC+) and immune cells (positive in >5% immune cells was PD-L1^IC+), and also used a combined positive score (CPS; number of PD-L1 staining cells relative to all viable tumor cells; > 1 was PD-L1⁺).

Results: In 73 MSI-H gastric carcinomas, MET overexpression was observed in 11 cases (15.1%). In all 11 cases with MET overexpression,MET amplification was not found. MET overexpression was not related to any of clinico-pathological variables and PD-L1 expression. However, the PD-L1 CPS tended to be higher in tumors that were MET positive. Although MET overexpression alone was not a prognostic indicator, combined MET overexpression/PD-L1 predictive models showed that patients with MET⁺/PD-L1⁺ showed the best prognosis for overall survival as compared to other groups.

Conclusion: MET overexpression was observed in 15% of MSI-H gastric carcinomas and was associated with high level expression of PD-L1.

Keywords: Gastric carcinoma; MET; Microsatellite instability-high; Programmed death-ligand 1.