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Annals of Oncology Advance Access originally published online on January 10, 2008
Annals of Oncology 2008 19(4):724-728; doi:10.1093/annonc/mdm576
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

gastrointestinal tumors

Human equilibrative nucleoside transporter 1 (hENT1) protein is associated with short survival in resected ampullary cancer

D. Santini1,*, G. Perrone2, B. Vincenzi1, R. Lai3, C. Cass3, R. Alloni4, C. Rabitti2, A. Antinori5, F. Vecchio6, S. Morini7, P. Magistrelli5, R. Coppola4, J. R. Mackey3 and G. Tonini1

1 Department of Medical Oncology
2 Department of Surgical Pathology, University Campus Bio-Medico, Rome, Italy
3 Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada
4 Department of Surgery, University Campus Bio-Medico, Rome
5 Department of Surgery
6 Department of Surgical Pathology, Catholic University of the Sacred Heart, Rome
7 Department of Biomedical Researches, Campus Bio-Medico University, Rome, Italy

* Correspondence to: Dr D. Santini, Department of Medical Oncology, University Campus Bio-Medico, via Emilio Longoni 81, 00155 Rome, Italy. Tel: +39-06-22541739; Fax: +39-06-22541520; E-mail: d.santini{at}unicampus.it

Background: Gemcitabine is an acceptable alternative to best supportive care in the treatment of advanced biliary tract cancers. The human equilibrative nucleoside transporter 1 (hENT1) is a ubiquitous protein and is the major means by which gemcitabine enters human cells. Moreover, recent reports indicate a significant correlation between immunohistochemical variations of hENT1 in tumor samples and survival after gemcitabine therapy in patients with solid tumors.

Materials and methods: We used immunohistochemistry to assess the abundance and distribution of hENT1 in tumor samples from radically resected cancer of the ampulla, and sought correlations between immunohistochemical results and clinical parameters including disease outcomes.

Results: In the 41 individual tumors studied, 12 (29.3%) had uniformly high hENT1 immunostaining. Statistical analysis showed a significant correlation between hENT1 and Ki-67 (P = 0.04). No statistical significant differences were found between immunohistochemical findings and patient characteristics (sex, age, and tumor–node–metastasis). On univariate analysis, hENT1 and Ki-67 expression were associated with overall survival (OS). Specifically, those patients with overexpression of hENT1 showed a shorter OS (P = 0.022) and those with high Ki-67 staining showed a shorter survival (P = 0.05).

Conclusions: hENT1 expression is a molecular prognostic marker for patients with resected ampullary cancer and holds promise as a predictive factor to assist in chemotherapy decisions.

Key words: ampullary cancer, hENTI, survival

Received for publication October 22, 2007. Revision received November 15, 2007. Accepted for publication November 20, 2007.


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