V-domain Ig-containing suppressor of T-cell activation (VISTA) is a novel
immune checkpoint protein and a potential immunotherapeutic target. However, its expression in
endometrial cancer has not been clearly defined. This study aimed to investigate VISTA expression and determine its associations with clinicopathological features, molecular subtypes, programmed cell death-
ligand 1 (PD-L1) expression, CD8+ T-cell count, and survival in a cohort of 839 patients with
endometrial cancer. Using direct sequencing of the polymerase epsilon (POLE)
exonuclease domain and immunohistochemistry for mismatch repair (MMR)
proteins and p53, we stratified
endometrial cancers into four molecular subtypes: POLE ultramutated, MMR-deficient, p53-mutant, and nonspecific molecular profile (NSMP). PD-L1, CD8, and VISTA were detected via immunohistochemistry. VISTA was expressed in the immune cells of 76.6% (643/839) of the samples and in the
tumor cells of 6.8% (57/839). VISTA positivity in the immune cells was frequent in
tumors staged I-III, those with positive PD-L1 or high CD8+ T-cell density, and those representing POLE ultramutated and MMR-deficient subtypes. Furthermore, VISTA positivity in
tumor cells was more frequent in clear cell
carcinoma samples. VISTA in immune cells was associated with improved survival in the entire cohort as well as in the endometrioid histology, stage I, PD-L1-negative, MMR-deficient, MMR-proficient, and high and low number of CD8+ T-cell-infiltrated
tumor subgroups. VISTA in immune cells was a prognostic factor overall, as well as in patients with endometrioid histology, independent of molecular subtype or CD8+ T-cell density. The data produced by this study, which was the largest to focus on VISTA expression in patients with
endometrial cancer to date, suggest that VISTA is a predictor of improved survival.