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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Antigens, CD34 / metabolism
  • Apoptosis / physiology
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology*
  • Female
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1 / biosynthesis*
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Inhibitor of Apoptosis Proteins
  • Ki-67 Antigen / metabolism
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Middle Aged
  • Neoplasm Proteins / metabolism
  • Neovascularization, Pathologic / metabolism
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Prognosis
  • Sex Factors
  • Survival Analysis
  • Survivin
  • Vascular Endothelial Growth Factor A / metabolism


  • Antigens, CD34
  • BIRC5 protein, human
  • Glucose Transporter Type 1
  • Hypoxia-Inducible Factor 1
  • Inhibitor of Apoptosis Proteins
  • Ki-67 Antigen
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Survivin
  • Vascular Endothelial Growth Factor A