PANCREATIC CANCER RESPONSE TO GEMCITABINE

Clin Cancer Res. 2009 Mar 24. [Epub ahead of print]

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Human Equilibrative Nucleoside Transporter 1 and Human Concentrative Nucleoside Transporter 3 Predict Survival after Adjuvant Gemcitabine Therapy in Resected Pancreatic Adenocarcinoma.

Maréchal R, Mackey JR, Lai R, Demetter P, Peeters M, Polus M, Cass CE, Young J, Salmon I, Devière J, Van Laethem JL.

Authors' Affiliations: Department of Gastroenterology and Hepato-Pancreatology, Gastrointestinal Cancer Unit, and Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium; Departments of Oncology and Physiology, University of Alberta, Cross Cancer Institute; Department of Pathology and Laboratory Medicine, University of Alberta, Edmonton, Alberta, Canada; Department of Hepato-Gastroenterology, Digestive Oncology Unit, University Hospital Ghent, Gent, Belgium; and Department of Medical Oncology, Centre Hospitalier Universitaire Sart-Tilman, Liège, Belgium.

PURPOSE: Gemcitabine is a promising adjuvant treatment for patients with resected pancreatic adenocarcinoma and its use in combination with radiotherapy is under exploration. Human equilibrative nucleoside transporter 1 (hENT1) and human concentrative nucleoside transporter (hCNT) 1 and 3 are the major transporters responsible for 2',2'-difluoro-2-deoxycytidine (gemcitabine) uptake into cells. The aim of this study was to determine patients' outcome according to the expression of hENT1 and hCNT3 in tumoral cells after postoperative gemcitabine-based chemoradiation regimen.EXPERIMENTAL DESIGN: We studied tumor blocks from 45 pancreatic adenocarcinoma patients treated with gemcitabine-based chemoradiation after curative resection and assessed hENT1 and hCNT3 expression using immunohistochemistry.RESULTS: When adjusted for the effects of lymph node ratio and tumor diameter, patients with high hENT1 expression had significantly longer disease-free survival and overall survival (OS) than patients with low expression, whereas high hCNT3 expression was only associated with longer OS. In a combined analysis, patients with two favorable prognostic factors (hENT1(high)/hCNT3(high) expression) had a longer survival (median OS, 94.8 months) than those having one (median OS, 18.7 months) or no (median OS, 12.2 months) favorable prognostic factor.CONCLUSIONS: Pancreatic adenocarcinoma patients with a high expression of hENT1 and hCNT3 immunostaining have a significantly longer survival after adjuvant gemcitabine-based chemoradiation. These biomarkers deserve prospective evaluation in patients receiving gemcitabine-based adjuvant therapy.