Evaluation of clear cell subtypes of ovarian and uterine malignancies with anti-PD-L1 and anti-PD1 immunohistochemical expression and their association with stage and survival

Objective Clear cell carcinomas (CCCs) of the ovary and uterus are rare and associated with poor prognosis. Information regarding expression of PD-1 positive tumor infiltrating lymphocytes or PD-L1 within gynecologic clear cell malignancies is limited and their role as a biomarker has not been explored. Methods This was a retrospective study of paraffin-embedded pure ovarian or uterine CCCs from 1992-2017. We assessed stage, endometriosis, and survival time. Immunohistochemical (IHC) staining for PD-1 associated TILs, PD-L1 percentage positivity, and PD-L1 Combined Positive Score (CPS) were performed. Results Of the 46 eligible patients, 35 were pure ovarian CCCs and 11 pure uterine CCCs. Most (29/46, 63.0%) were FIGO Stage I or II. We found 34.3% of ovarian tumors and 60% of the uterine tumors were PD-L1 CPS ≥1. PD-1 positive lymphocytes were present in 39.4% of ovarian tumors and 80% of the uterine tumors. When correlated to stage, ovarian cancer PD-L1 CPS was ≥1 in 28.6% stage I/II, 66.7% stage III, and 0% stage IV cancers (p=0.03) and PD-1 positive lymphocytes were found in 33.3% stage I/II, 66.7% stage III and 20% stage IV cancers (p=0.227). Within the uterine cohort, there were no significant differences in expression between stages. Multivariate analysis revealed no other significant correlations. There were no differences in overall survival for PD-L1 CPS positive versus negative cohorts among the ovarian cancer population (p = 0.79). Conclusions While limited by sample size, these findings suggest that more advanced ovarian cancer is less likely to express PD-L1 CPS, and that uterine cancers are more likely to have PD-1 positive lymphocytes than ovarian cancers. This biomarker information may better inform exploration of immune checkpoint therapy targeting.