Association of POLE-mutated and MSI endometrial cancers with an elevated number of tumor-infiltrating and peritumoral lymphocytes and higher expression of PD-L1.

Abstract

5511 Background: TCGA identified two groups of endometrial cancers with high mutation frequency: an ultramutated group of tumors which harbored mutations in polymerase e (POLE) and a hypermutated group with microsatellite instability (MSI). We hypothesized that these hypermutated tumors may harbor more neoantigens and thus stimulate a stronger immune response compared to tumors with low mutation frequency. In this regard, we evaluated whether hypermutated tumors are associated with an elevated number of tumor-infiltrating lymphocytes (TILs) and peritumoral lymphocytes and higher expression of the immune modulatory molecule PD-L1. Methods: We evaluated 4 POLE-mutated (determined via Sanger sequencing of mutational hotspots), 28 MSI-tumors and 32 microsatellite stable (MSS) endometrioid endometrial tumors. MSI status was determined using immunohistochemistry (IHC). IHC was performed for CD3, CD4, CD8, CD20, PD-1 and PD-L1 using standard protocols. For evaluation of TILs, a photomicrograph (40X) of the area ...