The HIF-2alpha/VEGF pathway activation in cutaneous capillary haemangiomas

Pathology. 2005 Apr;37(2):149-51. doi: 10.1080/00313020400025011.

Abstract

Aim: To investigate the pathogenesis of capillary haemangiomas, a common form of vascular malformation.

Methods: Twenty-five cutaneous capillary haemangiomas, excised from patients under 14 years of age, were studied immunohistochemically for endothelial cells, the angiogenic factors thymidine phosphorylase (TP) and vascular endothelial growth factor (VEGF), the proliferation index Ki-67, and the hypoxia inducible factors-1alpha (HIF-1alpha) and -2alpha (HIF-2alpha).

Results: Endothelial-lined channels reacted strongly with CD31 in all cases, clearly definining capillary spaces. Between 5 and 20% of the endothelial cells were Ki-67 positive, indicating an intense proliferative activity; more importantly, they consistently expressed VEGF and HIF-2alpha, and in many cases TP, but failed to react with HIF-1alpha.

Conclusion: It is suggested that the activation of the HIF-2alpha pathway and the consequent overexpression of VEGF by the endothelial cells are involved in the pathogenesis of cutaneous capillary haemangiomas.

MeSH terms

  • Adolescent
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Proliferation
  • DNA-Binding Proteins / biosynthesis
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Hemangioma, Capillary / blood supply*
  • Hemangioma, Capillary / metabolism*
  • Hemangioma, Capillary / pathology
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Immunoenzyme Techniques
  • Ki-67 Antigen / metabolism
  • Nuclear Proteins / biosynthesis
  • Skin Neoplasms / blood supply*
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Transcription Factors / biosynthesis*
  • Vascular Endothelial Growth Factor A / biosynthesis*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Ki-67 Antigen
  • Nuclear Proteins
  • Transcription Factors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • endothelial PAS domain-containing protein 1