Mismatch repair status and PD-L1 expression in clear cell carcinomas of the ovary and endometrium

Clear cell carcinoma represents a distinct histologic type of müllerian carcinoma that is resistant to conventional chemotherapy. Expression of programmed cell death ligand (PD-L1) has been associated with immune evasion in numerous tumor types and may be used to identify patients who will benefit from targeted immunotherapy, particularly in the setting of mismatch repair defects. We evaluated PD-L1 expression in 23 ovarian clear cell carcinomas and 21 endometrial clear cell carcinomas, and correlated expression with mismatch repair status. Tumor PD-L1 staining was seen in 43% of ovarian tumors and 76% of endometrial tumors, including 71% of cases (67% of ovarian and 75% of endometrial) with mismatch repair defects. Extensive tumoral staining (>50%) was seen in only one case (an endometrial case with MSH6 loss). However, tumoral PD-L1 expression remained common in mismatch repair-intact tumors and mismatch repair status was not significantly correlated with PD-L1 expression. The increased incidence of PD-L1 positivity in tumor cells (P=0.04) in endometrial vs ovarian clear cell carcinomas suggests differences in the tumor microenvironment of these histologically and molecularly similar tumors that may inform treatment options. These results suggest that clear cell histology may be a useful susceptibility marker for immunotherapy targeting the PD-1/PD-L1 axis irrespective of mismatch repair status, particularly in endometrial carcinomas.