Whole-section Immune and Molecular Phenotyping Identifies Distinct PD-L1 and p53 Phenotypic Subsets in Advanced Ovarian Carcinosarcoma

Ovarian carcinosarcoma (OCS) is a rare, aggressive malignancy with poor prognosis and limited treatment options. This study explored associations between programmed death-ligand 1 (PD-L1) expression, p53 phenotypic subclasses, mismatch repair (MMR) status, BRCA1/2 status, and clinical outcomes in advanced OCS. Twenty-one FIGO stage III–IV OCSs from a single institution were examined using whole-section immunohistochemistry for PD-L1, p53, and MMR proteins. Targeted next-generation sequencing for TP53 was carried out in selected cases. Clinical data were collected alongside germline/somatic BRCA1/2 results. PD-L1 was scored using the combined positive score or tumor proportion score. Median overall survival was 33 mo; 81% of patients experienced recurrence. PD-L1 positivity (combined positive score ≥1 and tumor proportion score ≥1%) was observed in 47.6% of tumors and demonstrated associations with improved survival. Aberrant p53 expression was identified in 95.2% of cases, with a potential association between the p53 null phenotype and increased PD-L1 expression in both carcinomatous and sarcomatous tumor components. All tumors were MMR proficient. BRCA1/2 mutations were identified in 28.6% of tested patients (germline or somatic), although incomplete testing limited interpretation. Whole-section assessment identified biologically distinct phenotypes within OCS. These findings provide a rationale for future translational studies aimed at identifying actionable clinical biomarkers and refining patient stratification in this challenging disease.