Prognostic role of human equilibrative transporter 1 (hENT1) in patients with resected gastric cancer |
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| Authors: | Daniele Santini Bruno Vincenzi Maria Elisabetta Fratto Giuseppe Perrone Raymond Lai Vincenzo Catalano Carol Cass Pier Adelchi Ruffini Chiara Spoto Pietro Muretto Sergio Rizzo Andrea Onetti Muda John R Mackey Antonio Russo Giuseppe Tonini Francesco Graziano |
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| Institution: | 1. Medical Oncology, University Campus Bio‐Medico, Rome, Italy;2. Surgical Pathology, University Campus Bio‐Medico, Rome, Italy;3. Cross Cancer Institute and Department of Oncology, University of Alberta, Edmonton, Alberta, Canada;4. Department of Medical Oncology, Azienda Ospedaliera “Ospedale San Salvatore”, Pesaro, Italy;5. Divisione Oncologia Medica Falck, Ospedale Niguarda Ca' Granda, Milano, Italy;6. Institute of Histopathology, Azienda Ospedaliera “Ospedale San Salvatore”, Pesaro, Italy;7. Department of Surgical and Oncological Sciences, Università degli Studi di Palermo, Palermo, Italy |
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| Abstract: | Nucleoside transporter proteins are specialized proteins that mediate the transport of nucleosides and nucleoside analog drugs across the plasma membrane. The human equilibrative nucleoside transporter 1 (hENT1) is a member of these proteins and mediates cellular entry of gemcitabine, cytarabine, and fludarabine. The hENT1 expression has been demonstrated to be related with prognosis and activity of gemcitabine‐based therapy in breast, ampullary, lung, and pancreatic cancer. We investigated the immunohistochemical expression of hENT in tumor samples from 111 patients with resected gastric adenocarcinoma, correlating these data with clinical parameters and disease outcomes. None of the patients received chemotherapy or radiation therapy before or after surgery as a part of an adjuvant or neoadjuvant program. On univariate survival analysis, the hENT1 expression was associated with overall survival (OS) and disease free survival (DFS). Specifically, those patients with overexpression of hENT1 showed a shorter OS (P = 0.021) and a shorter DFS (P = 0.033). Considering only the node positive patients, higher hENT levels were associated with significantly shorter median DFS (21.7 months; 95% CI 11.1–32.4) compared with patients with low expression of hENT1. The hENT1 expression was defined, in the lymph‐node positive patients, as an independent prognostic factor (P = 0.019). Furthermore, considering only patients with diffuse or mixed tumors and lymph‐node positive, the expression of hENT1 was strongly related with DFS and OS. Immunohistochemistry for the hENT1 protein carries prognostic information in patients with resected gastric cancer and holds promise as a predictive factor in chemotherapy decisions. J. Cell. Physiol. 223: 384–388, 2010. © 2010 Wiley‐Liss, Inc. |
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