Low expression of equilibrative nucleoside transporter 1 is associated with poor prognosis in chemotherapy-naïve pT2 gallbladder adenocarcinoma patients.

ABSTRACT

AIMS: Equilibrative nucleoside transporter 1 (ENT1) is the major transporter of the chemotherapeutic drug gemcitabine, the current therapy for advanced gallbladder cancer (GBC). ENT1 expression has been proposed as a predictive marker for gemcitabine-treated pancreatic cancer patients. The aim of study was to explore the value of ENT1 measurement in chemotherapy-naïve patients with advanced GBC. MATERIALS AND RESULTS: Immunohistochemistry for ENT1 was performed on 214 GBC samples from patients who had never undergone co-adjuvant or neo-adjuvant chemotherapy. Advanced GBC cases were divided into groups with low or high ENT1 expression. Kaplan-Meier tests were used for survival analyses. The Cox regression method was used to assess the association of ENT1 expression with overall survival (OS). Low ENT1 expression was associated with younger patient age (P = 0.03) and moderate-to-poor histological differentiation (P = 0.01). pT2 patients with low ENT1 expression had shorter median survival (17.3 versus 28.7 months) and lower OS (17.3% versus 33.3%, P < 0.05) than patients with high ENT1 expression. Low ENT1 expression was an independent prognostic factor for OS (P = 0.036). CONCLUSIONS: ENT1 is a prognostic marker for pT2 GBC patients. Additional studies are needed to determine whether ENT1 has predictive value for gemcitabine response in GBC.