Clear Cell Carcinoma of the Uterine Cervix; An Unusual HPV-Independent Tumor: Clinicopathological Features, PD-L1 Expression, and Mismatch Repair Protein Deficiency Status of 16 Cases

Abstract

Objective: Endocervical clear cell carcinoma (c-CCC) is a rare and HPV-independent adenocarcinoma type of cervix. Being usually resistant to conventional chemotherapy. Immunotherapy has recently been added as a preferred regimen as a second-line treatment option for programed cell death-ligand 1 (PD L1)-positive or mismatch repair (MMR) deficient cervical carcinomas. In this study, clinicopathological features, PD-L1 expression, and MMR deficiency status of c-CCCs were investigated.

Materials and Methods: Sixteen c-CCC diagnosed cases were included in this study. PD-L1 expression was evaluated using two different PD-L1 clones (22C3 and SP263). MMR deficiency status of the cases was evaluated using four MMR proteins (MLH1, PMS2, MSH2, and MSH6).

Results: Most of the c-CCC cases were presented as FIGO Stage I (68.75%). PD-L1 expression in either tumoral or tumor-infiltrating immune cells (TILs) was present in 62.5% (10/16) and 69% (11/16) of the 22C3 and SP263 clones, respectively. Most of the cases with high TIL density were also positive for PD-L1. The PD-L1 expression rate was less than 50% in most of the cases and 12.5% of the cases shared extensive PD-L1 staining. Overall, MMR deficiency was observed in 31.25% of the cases. Most of the MMR-deficient cases (80%) were PD-L1 positive.

Conclusion: Although our study cohort is limited, we have shown that PD-L1 expression and MMR deficiency can be found in c-CCCs in variable degrees. These findings suggest that accompanying TIL density and MMR deficiency could be used as candidates for predicting PD-L1 positivity for c-CCCs. However, to indicate the clinical importance of these findings, objective treatment outcomes of cases treated with immunotherapy should be seen.