The prognostic significance of human equilibrative nucleoside transporter 1 expression in patients with metastatic bladder cancer treated with gemcitabine-cisplatin-based combination chemotherapy

OBJECTIVE To evaluate the expression of the human equilibrative nucleoside transporter 1 (hENT1) and excision repair cross complementing 1 (ERCC1) as possible prognostic factors for patients with metastatic bladder cancer treated with gemcitabine-cisplatin-based combination chemotherapy. PATIENTS AND METHODS The present study retrospectively evaluated the expression of hENT1 and ERCC1 by immunostaining in chemo-naive primary bladder tumour specimens from 40 patients with metastatic bladder cancer who received treatment with gemcitabine-cisplatin-based combination chemotherapy at Wakayama Medical University Hospital and affiliated hospitals from May 2002 to July 2009. Immunohistochemistry on formalin-fixed, paraffin-embedded tissues was performed with specific hENT1 and ERCC1 antibodies scored by two pathologists who were blinded to clinical outcomes. The clinical and histopathological variables were analyzed to evaluate predictive values for survival. RESULTS The median survival time in patients with high and low hENT1 expression was 17.3 and 11.6 months, respectively (log-rank test, P = 0.003). This contrasted with the median survival in patients with high and low ERCC1 expressions, which did not differ significantly (high ERCC1, 13.6 months; low ERCC1, 17.1 months; P = 0.178). In univariate Cox regression analyses for pretreatment clinicopathological variables, performance status (P = 0.02) and hENT1 expression (P = 0.004), but not ERCC1 expression (P = 0.182), were associated with overall survival. Multivariate analysis using a Cox proportional hazards model showed that hENT1 expression was an independent prognostic factor (P = 0.008). CONCLUSION The data obtained in the present study show that high expression of hENT1 in tumour cells is associated with prolonged survival in patients with metastatic bladder cancer treated with gemcitabine-cisplatin-based combination chemotherapy.