Abstract

5025 Background: DNA damaging agents are the backbone of combination chemotherapy regimens for the treatment of advanced bladder cancer. We hypothesized that levels of DNA repair genes such as ERCC1 could predict survival in patients receiving platinum based therapy. Our previous work (Bellmunt J et al, Ann Oncol. 2007) showed that survival was significantly higher in advanced bladder cancer patients with low gene expression levels of ERCC1 measured by RT-qPCR (25.4 versus 15.4 months; p = 0.03). We aimed to confirm these findings using immunohistochemistry (IHC) in an independent cohort of advanced bladder cancer patients treated with cisplatin-based chemotherapy at our institution. Methods: Formalin-fixed paraffin-embedded tumor tissue was available from 51 patients. IHC stains for ERCC1 protein levels were scored as percentage and intensity of positive cells. ERCC1 staining was considered positive if detected in ≥1% tumor cells. The Kaplan-Meier method was used to calculate survival and the Cox proportional hazards model was used to examine the prognostic value of protein expression levels. Results: ERCC1 staining was negative in 60% of patients, weakly positive (1–10% positive cells) in 21% and strongly positive (>10% positive cells) in 19%. Median overall survival for all patients was 14.4m (95% CI 6.7–16.1m). Median disease-specific survival was significantly higher in patients negative for ERCC1 by IHC (12.6m versus 8.6m; p = 0.032). Conclusions: Our results using the more simple IHC technique confirm the prognostic value of ERCC1 expression in advanced bladder cancer. Patients with high expression of ERCC1 by IHC have a worse disease-specific survival than patients with no expression. A correlative study of IHC and RT-qPCR in both sets of samples is ongoing. No significant financial relationships to disclose.

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