Human equilibrative nucleoside transporter 1 expression is a strong independent prognostic factor in UICC T3-T4 pancreatic cancer patients treated with preoperative gemcitabine-based chemoradiotherapy

Background/purpose: We aimed to determine the relationship between the intratumoral expression of human equilibrative nucleoside transporter (hENT1), the main gemcitabine transporter into cells, and the outcome of gemcitabine-based chemoradiotherapy (Gem-CRT) in patients with International Union Against Cancer (UICC) T3-T4 pancreatic adenocarcinoma. Methods: The expressions of hENT1, thymidylate synthase (TS), and dihydropyrimidine dehydrogenase were immunohistochemically analyzed using the resected specimens from 55 patients (T3, 38 and T4, 17) who had received curative-intent resection after Gem-CRT. Results: The status of hENT1 expression (positive in 39 and negative in 16) was significantly associated with "clinical efficacy" (defined as more than 50% reduction of the serum carbohydrate antigen [CA] 19-9 level with stable disease [SD] or partial response [PR] according to the Response Evaluation Criteria in Solid Tumors [RECIST]) for Gem-CRT. The 1- and 3-year overall survival (OS) rates were significantly higher in the positive hENT1 expression group (82.9, 39.5%) than in the negative expression group (42.9, 14.3%) (p = 0.0037). According to combination analysis of hENT1 and TS expressions, the 1- and 3-year OS rates were significantly higher in the positive-low combination (89.1, 51.0%) group than in the negative-high group (66.7, 0%) (p = 0.023). Multivariate analysis revealed that positive hENT1 expression and R0 resection were significant prognostic factors for OS. Conclusions: The hENT1 expression in pancreatic adenocarcinoma strongly influences the outcome of preoperative Gem-CRT treatment. This biomarker could become a useful predictor of therapeutic effect for gemcitabine-based therapy in pancreatic cancer patients.