Objective Ovarian clear cell carcinoma (OCCC) is a rare type of epithelial ovarian cancer that behaves comparable to a distinct entity. Novel genomic and immunological profiling-based strategies targeting OCCC remain unavailable. ARID1A, which is one of the most frequently mutated genes in OCCC, could be a druggable target as well as a regulator of mismatch repair (MMR). Most of the mutated neoantigens in MMR-deficient cancers sensitize them to immune checkpoint blockade. However, the role and frequency of MMR deficiency in OCCC are still poorly understood. We aimed to evaluate the abnormal expression frequency of MMR and PD-L1 proteins in OCCC for identifying the effective OCCC population with immune checkpoint blockade.
Methods The study cohort comprised 113 patients with OCCC treated at a single institution. Protein expression levels in ARID1A, MLH1, PMS2, MSH2, MSH6, and PD-L1 were evaluated by immunohistochemistry (IHC). We investigated the correlations between immunoreactivity for MMR/PD-L1 and clinicopathological parameters including ARID1A status.
Results MMR proteins disappeared in two cases (1.8%), specifically those who had synchronous double cancer with endometrial carcinoma and a family history of Lynch syndrome-related tumor. PD-L1 expression was diffused in 17 cases (15.0%). The diffused PD-L1 expression was significantly associated with ARID1A expression loss (p = 0.003), but no other correlations existed between PD-L1 expression and clinical parameter.
Conclusions Although only few Japanese OCCC cases showed MMR deficiency as evaluated by IHC, immune checkpoint signals were activated even in MMR-intact OCCC, possibly through ARID1A interaction.
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