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


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.
Department of Pathology, Pontificia Universidad Católica de Chile, Santiago, Chile.|UC Centre for Investigational Oncology (CITO), School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, Santiago, Chile.
Jaime A
JA
Espinoza
Department of Pathology, Pontificia Universidad Católica de Chile, Santiago, Chile.|UC Centre for Investigational Oncology (CITO), School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, Santiago, Chile.
Patricia
P
García
Department of Pathology, Pontificia Universidad Católica de Chile, Santiago, Chile.|UC Centre for Investigational Oncology (CITO), School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, Santiago, Chile.
Carolina
C
Bizama
Department of Haematology and Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile.
José L
JL
Leal
Department of Pathology, School of Medicine, CEGIN-BIOREN, Molecular Pathology Laboratory, Universidad de La Frontera, Temuco, Chile.
Ismael
I
Riquelme
Department of Pathology, School of Medicine, CEGIN-BIOREN, Molecular Pathology Laboratory, Universidad de La Frontera, Temuco, Chile.
Helga
H
Weber
UC Centre for Investigational Oncology (CITO), School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|Department of Haematology and Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile.
Patricia
P
Macanas
Department of Pathology, Hospital Dr Sótero del Río, Santiago, Chile.
Gloria
G
Aguayo
Department of Digestive Surgery, Hospital Dr Sótero del Río, Santiago, Chile.
Eduardo
E
Viñuela
Department of Pathology, Pontificia Universidad Católica de Chile, Santiago, Chile.|UC Centre for Investigational Oncology (CITO), School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, Santiago, Chile.
Juan C
JC
Roa
UC Centre for Investigational Oncology (CITO), School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|Department of Haematology and Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile.
Bruno
B
Nervi
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D033721:Equilibrative Nucleoside Transporter 1 / Q000378:metabolism*; D005260:Female; D005704:Gallbladder / Q000000981:diagnostic imaging / Q000378:metabolism; D005706:Gallbladder Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D033721:Equilibrative Nucleoside Transporter 1; C438649:SLC29A1 protein, human; D003841:Deoxycytidine; D000093542:Gemcitabine
ENT1; SLC29A1; equilibrative nucleoside transporter 1; gallbladder cancer; gemcitabine