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J Natl Cancer Inst. 2014 Jan;106(1):djt347. doi: 10.1093/jnci/djt347. Epub 2013 Dec 3.

Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial.

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Affiliations of authors: Liverpool Cancer Research UK Cancer Trials Unit, Liverpool Cancer Research UK Centre, University of Liverpool, Liverpool, UK (WG, JPN, EG, TFC, PG, EC, CMH, CLR, FC, RJ); the Princess Margaret Hospital, Toronto, Canada (MJM); Manchester Academic Health Sciences Centre, Christie NHS Foundation Trust, School of Cancer and Enabling Sciences, University of Manchester, UK (JWV); Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK (DHP); Beatson West of Scotland Cancer Centre, Glasgow, UK (ACM); Glasgow Royal Infirmary, Glasgow, UK (RC); Hôpital Tenon, Université, Pierre et Marie Curie, Paris, France (FL); Austin Health, Melbourne, Australia (NCT); Prince of Wales Hospital and Clinical School University of New South Wales, New South Wales, Australia (DG); Nepean Cancer Centre and University of Sydney, Sydney, Australia (JS); Agia Olga Hospital, Athens, Greece (CD); Medical Oncology, Clatterbridge Centre for Oncology, Bebington, Merseyside, UK (DS); Department of Oncology, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden (BG); University Hospital, North Staffordshire, UK (MD); Freeman Hospital, Newcastle upon Tyne, UK (RMC); Service de Chirurgie Digestive et Viscérale, Hôpital Tenon, Paris, France (FL); Cross Cancer Institute and University of Alberta, Alberta, Canada (JRM, AGS); Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, UK (MRM); St James's University Hospital, Leeds, UK (AA); Department of Medicine A, University Medicine Greifswald, Greifswald, Germany (JM); Petz Aladar Hospital, Gyor, Hungary (AO); Departments of Surgery and Pathology and ARC-NET Research Center, University of Verona, Italy (AS, CB); Department of Surgery, University of Heidelberg, Heidelberg, Germany (MWB).



Human equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection.


Microarrays from 434 patients randomized to chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained with the 10D7G2 anti-hENT1 antibody. Patients were classified as having high hENT1 expression if the mean H score for their cores was above the overall median H score (48). High and low hENT1-expressing groups were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. All statistical tests were two-sided.


Three hundred eighty patients (87.6%) and 1808 cores were suitable and included in the final analysis. Median overall survival for gemcitabine-treated patients (n = 176) was 23.4 (95% confidence interval [CI] = 18.3 to 26.0) months vs 23.5 (95% CI = 19.8 to 27.3) months for 176 patients treated with 5-fluorouracil/folinic acid (χ(2) 1=0.24; P = .62). Median survival for patients treated with gemcitabine was 17.1 (95% CI = 14.3 to 23.8) months for those with low hENT1 expression vs 26.2 (95% CI = 21.2 to 31.4) months for those with high hENT1 expression (χ(2)₁= 9.87; P = .002). For the 5-fluorouracil group, median survival was 25.6 (95% CI = 20.1 to 27.9) and 21.9 (95% CI = 16.0 to 28.3) months for those with low and high hENT1 expression, respectively (χ(2)₁ = 0.83; P = .36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (χ(2)₁ = 0.37; P = .54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald χ(2) = 9.16; P = .003) but not 5-fluorouracil-treated (Wald χ(2) = 1.22; P = .27) patients.


Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.

[Indexed for MEDLINE]

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