Programmed death ligand-1 and MET co-expression is a poor prognostic factor in gastric cancers after resection
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Mi Jung Kwon1, Kab-Choong Kim2, Eun Sook Nam3, Seong Jin Cho3, Hye-Rim Park1, Soo Kee Min1, Jinwon Seo1, Ji-Young Choe1, Hye Kyung Lee1, Ho Suk Kang4 and Kyueng-Whan Min5
1Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Gyeonggi-do 431-796, Republic of Korea
2Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Gyeonggi-do 431-796, Republic of Korea
3Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul 134-701, Republic of Korea
4Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Gyeonggi-do 431-796, Republic of Korea
5Department of Pathology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Gyeonggi-do 11923, Republic of Korea
Mi Jung Kwon, email: [email protected]
Keywords: gastric cancer, programmed death ligand-1 protein, MET protein, prognosis, microsatellite instability
Received: March 31, 2017 Accepted: June 29, 2017 Published: July 19, 2017
Programmed death-ligand 1 (PD-L1) plays an essential protein for immune evasion, contributing to tumor development and progression. Recent studies have reported MET as an upregulator for PD-L1 overexpression through an oncogenic pathway. However, an association between PD-L1 expression with MET has not been reported in gastric cancer.The prognostic significance of PD-L1 and its association with Epstein-Barr virus (EBV), microsatellite instability (MSI), and mucin phenotype remain controversial.
We performed in situ hybridization for EBV-encoded RNA and immunohistochemistry in tissue microarrays for 394 gastric cancers. A multiplex polymerase chain reaction with five quasimonomorphic markers was performed for MSI.
PD-L1 expression was observed in 123 cases (31.2%), and clinicopathological features such as MET overexpression, high pT stage, and a lack of lymphatic invasion represent significant risk factors associated with PD-L1 overexpression in gastric cancers. No associations of EBV, MSI, or mucin phenotype with PD-L1 expression were statistically significant. PD-L1 expression was a strong indicator for worse overall survival (OS) but borderline significant in disease-free survival (DFS). A combined analysis of PD-L1 and MET expression indicated that the PD-L1+/MET+ subgroup showed the worst prognosis when compared to the PD-L1-/MET- subgroup, which had the best clinical outcome. Furthermore, PD-L1 overexpression exhibited poor prognosis in terms of both OS and DFS in EBV-negative, microsatellite stable, and intestinal mucin phenotype tumors. In conclusion, this is the first study to evaluate the overexpression of MET as a risk factor for PD-L1 positivity in gastric cancer tissue as well as the reliability and prognostic relevance of PD-L1/MET co-expression after surgery.
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