Programmed Death Ligand 1 Expression Among 700 Consecutive Endometrial Cancers: Strong Association With Mismatch Repair Protein Deficiency.

Abstract

This study aims to determine the prevalence of programmed death ligand 1 (PD-L1) expression in endometrial carcinoma (EC) and determine clinical and pathological associations. Immunohistochemistry for PD-L1 was performed on sections of a triple-core tissue microarray of 700 ECs. Positive PD-L1 expression, defined as 1% of cells staining positive, was evaluated in tumor and stromal compartments. Using age-adjusted logistic regression, we estimated odds ratios and 95% confidence intervals for associations between PD-L1 expression (overall and by staining compartment) with clinical and tumor characteristics. Kaplan-Meier plots and log-rank tests were used to evaluate associations between PD-L1 expression and EC-specific survival. PD-L1 expression was observed in 100 cases (14.3%), including 27 (3.9%) with expression in tumor cells only, 35 (5.0%) with expression in both tumor cells and stroma, and 38 (5.4%) with expression in stroma only. Expression was observed in ECs of different histologic types. Tumors characterized by loss of mismatch repair proteins were significantly associated with tumoral PD-L1 expression (P < 0.0001), but not with stromal PD-L1 expression. Both tumoral and stromal PD-L1 expressions were associated with high-grade endometrioid histology, nonendometrioid histology, and lymphovascular space invasion. We observed no significant associations between PD-L1 expression and EC-specific survival. PD-L1 is expressed in a significant proportion of EC and is associated with mismatch repair deficiency, potentially representing a mechanism of tumor immune evasion and a therapeutic target in EC.