title: The HIF-2alpha/VEGF pathway activation in cutaneous capillary haemangiomas.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pathology, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr
authors: Alexandra
authors: A
authors: Giatromanolaki
authors: Vasiliki
authors: V
authors: Arvanitidou
authors: Athanasios
authors: A
authors: Hatzimichael
authors: Constantinos
authors: C
authors: Simopoulos
authors: Efthimios
authors: E
authors: Sivridis
mesh_terms: D000293:Adolescent; D051792:Basic Helix-Loop-Helix Proteins; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D018324:Hemangioma, Capillary / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis; D012878:Skin Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human; C467484:VEGFA protein, human