Molecular Interplay Between PTEN, ARID1A, PD-L1 and MMR in Asian Ovarian Clear Cell Carcinoma: Implications for Immunotherapy Response and Patient Stratification

Background: Ovarian clear cell carcinoma (OCCC) represents a distinct histological subtype with high prevalence in Asian populations and poor chemotherapy response. PTEN, ARID1A, PD-L1, and mismatch repair (MMR) proteins have demonstrated clinical significance in cancer progression and treatment response. This study investigated molecular interactions between these biomarkers in Asian OCCC patients. Methods: Immunohistochemical analysis was performed on tissue microarrays from 69 OCCC cases. Expression of PTEN, ARID1A, PD-L1, and four MMR proteins were evaluated alongside clinical data. Results: We observed high prevalence of PTEN loss (78.3%) and ARID1A deficiency (48.8%), with PD-L1 expression in 26.1% and MMR deficiency in 10.1% of cases. All PD-L1-positive tumors demonstrated concurrent PTEN loss (p=0.007). MMR deficiency was significantly associated with ARID1A loss (p=0.049). PTEN loss correlated with worse progression-free survival in early-stage disease (p=0.039). Concurrent retention of both ARID1A and PTEN occurred in only 3 cases (6.8%). Conclusions: PTEN and ARID1A alterations represent early pathogenic events in Asian OCCC, with PTEN loss significantly impacting progression-free survival in early-stage disease. The correlation between PTEN loss and PD-L1 expression, alongside the association between ARID1A and MMR deficiency, provides new insight into OCCC's immunological landscape and potential therapeutic vulnerabilities.