Comparison of PD-L1, VISTA, LAG-3, and GAL-3 Expressions and Their Relationships to Mismatch Repair Protein and p53 Expression in 529 Cases of Endometrial Carcinoma.

Abstract

The aim of this study is to evaluate the expressions of programmed death-ligand 1 (PD-L1), V-domain Ig suppressor of T-cell activation (VISTA), lymphocyte activation gene-3 (LAG-3), and galectin-3 (GAL-3), in mismatch repair-deficient (MMRd)/MMR-proficient and abnormal p53 expressing endometrial carcinomas and their relationship with clinical-histopathological features. Patients who underwent surgery for endometrial carcinoma between January 2008 and December 2018 were included in the study. Immunohistochemical analysis of MLH1, PMS2, MSH2, MSH6, p53, PD-L1, VISTA, LAG-3, and GAL-3 was performed on the tissue samples of microarray. A total of 529 patients were included. MMRd and p53-mutant tumors accounted for 31.5% and 11.5% of cases, respectively. PD-L1 and LAG-3 expressions in the MMRd and p53-mutant groups were higher than in the MMR-proficient group (P < 0.001). GAL-3 expression in the MMR-proficient group was statistically higher than in the MMRd and p53-mutant groups (P < 0.001). Mean age, grade, International Federation of Gynecology and Obstetrics stage, lymphovascular invasion, and lymph node metastasis were significantly higher in the p53-mutant group (P < 0.001). In the group with PD-L1 expression, nonendometrioid histologic type, tumor grade, and lymphovascular invasion were significantly higher (P < 0.001). Tumor grade, lymphovascular invasion, lymph node metastasis, and microcystic, elongated and fragmented pattern of invasion were significantly higher in the group with high VISTA expression (P < 0.05). Tumor grade was significantly higher in the group with LAG-3 expression (P < 0.001). Immunohistochemically determined subgroups and PD-L1, VISTA, LAG-3, and GAL-3 expression levels may be useful indicators of molecular features, and clinical outcomes also may have important implications for the development of targeted therapies in endometrial carcinoma.