Immunoexpression of P53, KRAS, BRAF, PTEN and PIK3CA in ovarian epithelial carcinomas

Background: Epithelial ovarian carcinomas (EOCs) constitute the majority of ovarian malignancies and display distinct molecular profiles based on histologic subtype. The dualistic model classifies EOCs into Type I and Type II tumors, based on differing morphologic and molecular characteristics. While TP53 mutations predominate in Type II tumors, Type I tumors frequently harbor alterations in genes such as KRAS, BRAF, PTEN, and PIK3CA. Immunohistochemistry (IHC) serves as a cost-effective and accessible surrogate for detecting underlying molecular abnormalities This is study to evaluate the immunohistochemical expression of P53, KRAS, BRAF, PTEN, and PIK3CA across major histological subtypes of ovarian epithelial carcinomas and assess their correlation with tumor type and known mutation frequencies.. Materials and Methods: This prospective cross-sectional study included 52 histologically confirmed cases of epithelial ovarian carcinoma. Immunohistochemistry was performed on 73 tumor samples (including bilateral cases) using standard protocols. Marker expression was evaluated and classified based on established IHC scoring criteria. Tumors were categorized into Type I (P53 wild-type) and Type II (P53 mutant) according to the dualistic model. Statistical analysis was performed using Chi-square test. Results: High-grade serous carcinoma (HGSC) was the most common subtype (65.4%), followed by low-grade serous, mucinous, and endometrioid carcinomas. Mutant P53 expression was seen in 70.8% of HGSC, validating its utility as a surrogate marker for TP53 mutation. KRAS was positive in a majority of Type I and Type II tumors (62.2% and 69.4%, respectively). BRAF expression was limited to Type I tumors, with 40% positivity in low-grade serous carcinoma. PTEN loss was more frequent in Type I tumors (59.5%) compared to Type II (41.7%). PIK3CA expression was significantly higher in Type I tumors (67.6%) compared to Type II (47.2%) (p = 0.042). Discordant immunoexpression was observed in some bilateral tumors. Conclusion: The study supports the dualistic model of ovarian carcinogenesis, with distinct immunoprofiles observed between Type I and Type II tumors. PIK3CA showed significant discriminatory value and may be useful alongside P53 for molecular classification. However, discrepancies with known mutation frequencies highlight the need for further standardization of IHC protocols and validation with molecular studies.