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

Abstract

Ovarian clear cell carcinoma (OCCC) represents a distinct histological subtype with a high prevalence in Asian populations and poor chemotherapy response. This study investigated molecular interactions between phosphatase and tensin homolog (PTEN), AT-rich interactive domain 1A (ARID1A), programmed death-ligand 1 (PD-L1), and mismatch repair (MMR) proteins in Asian patients with OCCC. Immunohistochemical analysis was performed on tissue microarrays from 69 OCCC cases. The expression of PTEN, ARID1A, PD-L1, and four MMR proteins was evaluated alongside clinical data. A 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, was observed. 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 (PFS) in early-stage disease (p = 0.039). PTEN and ARID1A alterations represent early pathogenic events in Asian OCCC, with PTEN loss significantly impacting PFS in early-stage disease. The correlation between PTEN loss and PD-L1 expression, alongside ARID1A-MMR deficiency association, provides insights into OCCC’s immunological landscape and therapeutic vulnerabilities.