Human equilibrative nucleoside transporter 1 and human concentrative nucleoside transporter 3 predict survival after adjuvant gemcitabine therapy in resected pancreatic adenocarcinoma.

Abstract

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.

• Authors: Raphaël Maréchal, John R Mackey, Raymond Lai, Pieter Demetter, Marc Peeters, Marc Polus, Carol E Cass, James Young, Isabelle Salmon, Jacques Devière, Jean-Luc Van Laethem
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 15 Issue 8 Pg. 2913-9 (Apr 15 2009) ISSN: 1078-0432 [Print] United States
• PMID: 19318496 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Equilibrative Nucleoside Transporter 1
• Membrane Transport Proteins
• cif nucleoside transporter
• Deoxycytidine
• Gemcitabine

Topics

• Adenocarcinoma (drug therapy, mortality, radiotherapy)
• Adult
• Aged
• Aged, 80 and over
• Chemotherapy, Adjuvant
• Clinical Trials, Phase I as Topic
• Deoxycytidine (administration & dosage, analogs & derivatives, therapeutic use)
• Equilibrative Nucleoside Transporter 1 (metabolism)
• Female
• Follow-Up Studies
• Humans
• Male
• Membrane Transport Proteins (metabolism)
• Middle Aged
• Multivariate Analysis
• Neoplasm Recurrence, Local
• Pancreatic Neoplasms (drug therapy, mortality, radiotherapy)
• Gemcitabine