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Int J Oncol. 2007 Jun;30(6):1359-67.

Expression of hypoxia-inducible factor-1 alpha and associated proteins in pancreatic ductal adenocarcinoma and their impact on prognosis.

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1
Department of General Surgery, Affiliated First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, PR China.

Abstract

The aim of this study was to assess the significance of expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and associated proteins in pancreatic ductal adenocarcinoma (PDA) and their impact on prognosis. Expression of HIF-1alpha, vascular endothelial growth factor (VEGF), glucose transporter-1 (Glut-1), survivin, CD34 and Ki-67 and apoptotic cells was demonstrated by immunohistochemistry or TUNEL in 58 PDAs and 20 normal pancreatic tissue samples. Our results show positivity of HIF-1alpha, VEGF, Glut-1 and survivin in 70.7%, 77.6%, 67.2% and 84.5% of the patients with PDA, respectively, which is significantly higher than in the normal counterparts. Expression of HIF-1alpha correlated positively with VEGF and Glut-1 expression but not with survivin. Strong HIF-1alpha expression associated with decreased apoptotic index and increased intratumoral microvessel density. Higher HIF-1alpha, VEGF and Glut-1 expression significantly associated with advanced tumor stage and lymph node metastasis. Patients with high HIF-1alpha, VEGF and Glut-1 expressing tumors had a poorer overall survival. Furthermore, Cox regression analysis showed that HIF-1alpha is a prognostic marker of borderline significance while VEGF was important in predicting poor outcome. These results suggest that over-expression of HIF-1alpha may play an important role in cancer progression through up-regulation of VEGF and Glut-1 in PDA patients. HIF-1alpha and VEGF are potential candidates for predicting survival.

PMID:
17487356
[Indexed for MEDLINE]

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