The relationship of PD-L1/PD-L2 expression and microsatellite instability with tumor variables and prognosis in gastric carcinomas.

Gastric cancers are 5th among the most common cancers and 3rd in cancer-related deaths. Gastric cancer is usually diagnosed at an advanced stage, and 5-year survival is less than 20% with very limited cytotoxic chemotherapy. The addition of targeted drugs to chemotherapeutic agents in therapy has provided modest improvement in overall survival, but unfortunately the disease prognosis remains poor. Emerging data suggest that patients' prognosis depends not only on disease stage, but also on specific molecular and histopathological tumor characteristics. Two detailed genomic characterizations of gastric cancer have been recently developed by the Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG), proving that gastric cancer is a complex and heterogeneous disease. Interestingly, the MSI-H subgroup was defined in both of these classifications. Also, in recent years, immunotherapy has become very popular in the field of cancer treatment around the world. Expression of immunomodulatory proteins such as PD-L1 and PD-L2 in neoplastic cells has been described in many malignancies and has been associated with an aggressive clinicopathological course and poor prognosis. In our study, 104 gastric adenocarcinoma cases diagnosed between February 2011 and May 2019 in Baskent University Faculty of Medicine Ankara Hospital Pathology Department, who underwent total and subtotal gastrectomy, were analyzed retrospectively. In addition to clinicopathological parameters, the cases were evaluated together with PD-L1, PD-L2, MSH2, MSH6, PMS2, PMS6 applied immunohistochemically. In our case group, a positive correlation was found between PD-L1 expression in the tumor and survival. A statistically significant relationship was also found between PD-L1 expression in peripheral tumor immune cells and overall survival data. A negative correlation was found between increased PD-L1 staining in peri-tumor inflammatory cells and survival. Cases expressing PD-L2 were found to have longer survival times, and a significant correlation was found between expression and tumor diameter and tumor stage. In our study, MSH2-MSH6 and PMS2-MLH1 dimers were evaluated separately and a relationship was found between MSH2-MSH6 instability and overall survival. MSH2-MSH6 stable cases have been observed to have longer survival times. It was noted that PMS2-MLH1 unstable cases had larger tumor diameters. In addition, when we evaluated the expression of PD-L1 in microsatellite unstable tumors and immune cells around the tumor, survival was found to be significantly higher in cases with PD-L1 expression. In our study, where we concluded that PD-L2, which is a very new marker in gastric cancers, and PD-L1 expression in peripheral tumor immune cells are good prognostic markers, and MSH2-MSH6 instability is bad prognostic markers, we thought that the use of these markers in the pathology routine could help predict survival.