Abstract 904: EGFR expression predicts recurrence in patients undergoing adjuvant chemotherapy for advanced bladder cancer

Abstract

Abstract Epidermal growth factor receptor (EGFR) overexpression has been associated with bladder cancer progression and poor clinical outcomes. In vivo studies have linked EGFR subcellular trafficking and chemo-resistance to cisplatin-based protocols in other tumor types. This has not been studied in the clinical adjuvant setting in bladder cancer. In this study, we aimed to investigate the prognostic significance of EGFR expression in patients receiving adjuvant chemotherapy following radical cystectomy for advanced bladder cancer. Mansoura Urology and Nephrology Center database was reviewed. Patients treated with radical cystectomy and thereafter completed adjuvant chemotherapy for adverse pathological features or node positive diseases were identified. Patients who underwent palliative cystectomy, those with histological diagnosis other than pure transitional cell carcinoma and patients who received adjuvant radiotherapy were excluded. Immunohistochemical analysis for EGFR expression was performed on archived bladder specimens. The relationship of EGFR expression and clinical outcomes was assessed. In vitro studies were performed to determine whether EGFR expression associates with resistance to chemotherapeutic reagents. The study included 58 patients. Mean age was 57 years. All patients had pathologic stage T2 or greater. Majority of patients had node positive disease (n=53, 91%). Mean follow up was 26.61 months. EGFR was overexpressed in 25 cystectomy specimens (43%). Kaplan Meyer analysis revealed that EGFR over-expression significantly correlated with disease recurrence (p=0.021). Cox proportional hazard modeling identified EGFR overexpression as an independent predictor for disease recurrence (p=0.04). In vitro functional analysis demonstrated that EGFR expression level altered response to cisplatin-induced apoptosis, and that inhibition of EGFR enhanced sensitization of bladder cancer cells to cisplatin-induced apoptosis. In summary, our findings suggest that EGFR overexpression is associated with disease recurrence following adjuvant chemotherapy for advanced bladder cancer. EGFR status may help predict prognosis and select patients for adjuvant chemotherapy. Citation Format: Ahmed Mansour, Mona Abdulreheem, Mamdouh Elsherbeeny, Mohammed Sultan, Ahmed Shokeir, Ahmed Mosbah, Hassan Abol-Enein, Taeeun Park, Hyung Kim, Jayoung Kim. EGFR expression predicts recurrence in patients undergoing adjuvant chemotherapy for advanced bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 904. doi:10.1158/1538-7445.AM2014-904