Ekspresi Protein 53 (P53) Sebagai Prediktor Agresivitas Pada High-Grade Serous Ovarian Carcinoma

Abstract

Background: High-Grade Serous Ovarian Carcinoma (HGSC) is the most dominant histological subtype of epithelial ovarian cancer and exhibits highly aggressive biological behavior. The high mortality rate associated with HGSC is exacerbated by delayed clinical diagnosis and a high propensity for developing resistance to platinum-based chemotherapy. At the molecular level, abnormalities in tumor-suppressor pathways—mediated by somatic mutations in the TP53 gene—are found in nearly all HGSC cases (accounting for approximately 96%). Objective: This analytical study aimed to examine and analyze the correlation between various mutant p53 expression patterns (immunophenotypes) and key parameters of tumor aggressiveness, specifically FIGO clinical stage, the presence of lymphovascular invasion (LVI), and the cellular proliferation index as measured by Ki-67 expression. Methods: A retrospective analytical cohort study was conducted on 68 paraffin-embedded tissue samples from patients conclusively diagnosed with HGSC via histopathological examination at the Department of Anatomical Pathology over the past five years. p53 protein expression was evaluated using IHC staining and categorized into abnormal/mutant pattern groups (comprising overexpression and complete absence/null subtypes) and a normal/wild-type pattern group. Results: Mutant-type p53 protein expression patterns were overwhelmingly predominant, observed in 64 out of 68 cases (94.1%). The distribution of these abnormal immunophenotypic variants consisted of an overexpression pattern in 42 cases (61.8%) and a null phenotype pattern in 22 cases (32.3%), whereas a normal/wild-type pattern was observed in only 4 cases (5.9%). Statistical analysis demonstrated that the presence of mutant p53 expression patterns—particularly the null phenotype subtype—showed a linear relationship and highly significant correlation with advanced FIGO clinical stage (III/IV) (p < 0.05), the presence of lymphovascular invasion (p < 0.02), and a very high Ki-67 proliferation index (≥ 60%; p < 0.01).

Conclusion: The mutant p53 expression profile, specifically the null phenotype, serves as a strong independent predictor of clinical and biological aggressiveness in patients with HGSC. Routine assessment and reporting of p53 immunohistochemical (IHC) pattern subtypes are highly recommended during pathological evaluation to facilitate prognostic risk stratification and the application of targeted therapies.