Jaime A Espinoza1,2,3, Patricia García1,2,3, Carolina Bizama1,2,3, José L Leal4, Ismael Riquelme5, Helga Weber5, Patricia Macanas2,4, Gloria Aguayo6, Eduardo Viñuela7, Juan C Roa1,2,3, Bruno Nervi2,4. 1. Department of Pathology, Pontificia Universidad Católica de Chile, Santiago, Chile. 2. UC Centre for Investigational Oncology (CITO), School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile. 3. Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, Santiago, Chile. 4. Department of Haematology and Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile. 5. Department of Pathology, School of Medicine, CEGIN-BIOREN, Molecular Pathology Laboratory, Universidad de La Frontera, Temuco, Chile. 6. Department of Pathology, Hospital Dr Sótero del Río, Santiago, Chile. 7. Department of Digestive Surgery, Hospital Dr Sótero del Río, Santiago, Chile.
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.
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 cancerpatients. 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.
Authors: Bruno Vincenzi; Silvia Stacchiotti; Paola Collini; Francesco Pantano; Carla Rabitti; Giuseppe Perrone; Michele Iuliani; Alfonso Baldi; Giuseppe Badalamenti; Roberta Sanfilippo; Daniele Santini; Andrea Onetti Muda; Alessandro Gronchi; Paolo Casali; Angelo Paolo Dei Tos; Giuseppe Tonini Journal: Br J Cancer Date: 2017-06-22 Impact factor: 7.640