ERCC1 as a Prognostic and Predictive Biomarker for Urothelial Carcinoma of the Bladder following Radical Cystectomy.

Overview

abstract

PURPOSE: ERCC1 is the key enzyme of the nucleotide excision repair pathway, which maintains genomic stability. ERCC1 has been proposed as a prognostic and predictive biomarker for patients with urothelial carcinoma of the bladder but there are limited data on patients after radical cystectomy. MATERIALS AND METHODS: ERCC1 was evaluated by immunohistochemistry in radical cystectomy specimens of 432 patients. Associations with disease-free and cancer specific survival, and the effect of adjuvant cisplatin based chemotherapy were assessed. Further, ERCC1 mRNA expression and in vitro sensitivity to cisplatin were correlated in 25 bladder urothelial carcinoma cell lines. RESULTS: ERCC1 was expressed in 308 tumors (71.3%). There was no association with clinicopathological variables (each p >0.3). Median postoperative followup was 128 months. On multivariable analyses patients with ERCC1 positive tumors had significantly better disease-free survival (HR 0.70, p = 0.028) and cancer specific survival (HR 0.70, p = 0.032) than those with ERCC1 negative tumors. Discrimination of the multivariable models increased by 0.7% to 0.9% following the inclusion of ERCC1. There was no modification of the effect of adjuvant cisplatin based combination chemotherapy by ERCC1 status (p = 0.38 and 0.88, respectively). There was also no correlation between ERCC1 and sensitivity to cisplatin in vitro (R(2) = 0.02, p = 0.46). CONCLUSIONS: ERCC1 may be a prognostic biomarker for urothelial carcinoma of the bladder. Patients with ERCC1 positive tumors may have better survival than those with ERCC1 negative tumors. However, the efficacy of adjuvant cisplatin based chemotherapy appears to be unrelated to ERCC1 status.