3 years ago

MET is overexpressed in microsatellite instability-high gastric carcinoma

Jongmin Sim, You Jeong Heo, Hyunsik Bae, Hyeong Chan Shin, Binnari Kim, Junhun Cho, Seung Tae Kim, Jeeyun Lee, Won Ki Kang, Kyoung-mee Kim

Publication date: Available online 12 November 2018

Source: Pathology - Research and Practice

Author(s): Jongmin Sim, You Jeong Heo, Hyunsik Bae, Hyeong Chan Shin, Binnari Kim, Junhun Cho, Seung Tae Kim, Jeeyun Lee, Won Ki Kang, Kyoung-Mee Kim

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-L1TC+) and immune cells (positive in >5% immune cells was PD-L1IC+), 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.

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