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


METHODS
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.
Maréchal
Raphaël
R
Department of Gastroenterology and Hepato-Pancreatology, Gastrointestinal Cancer Unit, and Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. rmarecha@ulb.ac.be
Mackey
John R
JR
Lai
Raymond
R
Demetter
Pieter
P
Peeters
Marc
M
Polus
Marc
M
Cass
Carol E
CE
Young
James
J
Salmon
Isabelle
I
Devière
Jacques
J
Van Laethem
Jean-Luc
JL