Expression of HIF-2alpha/EPAS1 in hepatocellular carcinoma

World J Gastroenterol. 2004 Feb 15;10(4):525-30. doi: 10.3748/wjg.v10.i4.525.

Abstract

Aim: To investigate the expression of hypoxia-inducible factor (HIF)-2alpha/endothelial PAS domain protein1 (EPAS1) in hepatocellular carcinoma (HCC).

Methods: Expression of HIF-2alpha/EPAS1 was investigated immunohistochemically on paraffin-embedded sections from 97 patients with HCC. To further confirm that HIF-2alpha/EPAS1 in HCC tissues also correlated with angiogenesis, a parallel immunohistchemistry study of vascular endothelial growth factor (VEGF) was performed on these 97 cases.

Results: HIF-2alpha/EPAS1 could be detected in 50 of 97 cases (51.6%), including 19 weakly positive (19.8%), and 31 strongly positive (31.1%), the other 47 cases were negative (48.4%). The expression of HIF-2alpha/EPAS1was significantly correlated with tumor size, capsule infiltration, portal vein invasion, and necrosis. A parallel immunohistochemical analysis of VEGF demonstrated its positive correlation with capsule infiltration, portal vein invasion, and HIF-2alpha/EPAS1 overexpression, which supported the correlation of HIF-2alpha/EPAS1up-regulation with tumor angiogenesis. No apparent correlation was observed between HIF-2alpha/EPAS1 and capsular formation, presence of cirrhosis, and histological grade.

Conclusion: HIF-2alpha/EPAS1 is expressed in most of HCC with capsular infiltration and portal vein invasion, which indicates a possible role of HIF-2alpha/EPAS1 in HCC metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Basic Helix-Loop-Helix Transcription Factors
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / secondary
  • Female
  • Humans
  • Immunohistochemistry
  • Liver Cirrhosis / pathology
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Portal Vein / pathology
  • Trans-Activators / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Trans-Activators
  • Vascular Endothelial Growth Factor A
  • endothelial PAS domain-containing protein 1