RAD51, BRCA1, AND BRCA2: CAN BE PROMISING PROGNOSTIC FACTORS AND NEW THERAPY TARGETS FOR CLEAR CELL RENAL CELL CARCINOMA PATIENTS?

Amira M. ABD EL MAGED, Heba Mahmoud ABDELGELEEL, Eslam G. ABOZAID, Amira H. HANNA, Hanan Lotfy MOHAMMED

Journal of Urological Surgery - 2026;13(3):186-198

Menoufia University Faculty of Medicine, Shebin El Kom, Egypt

 

Objective: Clear cell renal cell carcinoma (ccRCC) is the predominant form of renal cell carcinoma, distinguished by its genetic alterations that affects the tumor's progression and response to treatment. RAD51, BRCA1, and BRCA2 are fundamental components of the homologous recombination (HR) DNA repair system, which is vital for preserving genomic stability. Yet, data regarding their expression pattern and potential role in ccRCC development and progression remain unclear. The aim of this work was to study the immunohistochemical expression of RAD51, BRCA1, and BRCA2 in ccRCC and to investigate the correlation between their expression levels and the clinical outcomes of patients with ccRCC. Materials and Methods: Across-sectional study has been performed at Zagazig University's Faculty of Medicine using data from the Pathology Department archives between January 2020 and December 2023 through analyzing 76 ccRCC specimens who underwent either a total (56 cases) or partial nephrectomy (20 cases) to determine the RAD51, BRCA1, and BRCA2 immunohistochemical expressions and comparing these with clinicopathologic parameters and survival. Results: High nuclear expression of RAD51 was detected in 42.1% of cases and was significantly associated with poor prognostic indicators, including advanced tumor stage, lymphatic spread, distant metastasis, and recurrence. High nuclear expression of BRCA1, BRCA2, and both proteins was detected in 51.3%, 35.5%, and 27% of cases, respectively, and their immune expression was significantly correlated with favorable prognostic indicators, including early tumor stage and absence of lymphatic spread. High RAD51 expression showed significant indirect correlations with BRCA1 expression and with the co-expression of BRCA1 and BRCA2. Using Kaplan-Meier analysis, patients with high RAD51 and low BRCA1 expression had shorter disease-free survival and overall survival. Conclusion: This research emphasizes the significance of RAD51, BRCA1, and BRCA2 in the progression of ccRCC. Elevated RAD51 levels alongside reduced BRCA1 and BRCA2 expression are associated with more aggressive tumors, suggesting their potential as immunohistochemical prognostic indicators and providing insights into novel therapeutic approaches for patients with ccRCC.