title: Support for the hypoxia theory in the pathogenesis of infantile haemangioma.
abstract: BACKGROUND
  The pathogenesis of infantile haemangioma (IH) is unknown. Several mechanisms have been proposed, including hypoxia, which triggers upregulation and stabilization of hypoxia-inducible factor (HIF)1α. HIF1α stimulates downstream transcription of target genes that enhance angiogenesis.
  
  
  OBJECTIVE
  To identify possible involvement of hypoxia in the pathogenesis of IH, as hypoxia signalling constitutes a potential therapeutic target.
  
  
  METHODS
  IH tissue samples collected during the period 1991-2011 (preserved in paraffin wax) were immunohistochemically analysed for HIF1α and the known HIF1α targets: BCL2/adenovirus E1B kD-interacting protein family member 3 (BNIP3), carbon anhydrase (CA)-IX, glucose transporter (GLUT)-1, phosphorylated protein kinase B (pAKT), phosphorylated S6 protein (pS6) and vascular endothelial growth factor (VEGF). Four observers independently assessed the findings.
  
  
  RESULTS
  Of the 10 IH samples, 2 appeared to be in the growth phase. In all samples, GLUT-1, BNIP3, pAKT and VEGF were positive, CA-IX was weakly positive, and HIF1α was negative. pS6 was positive in 9/10 cases and negative in 1/10.
  
  
  CONCLUSIONS
  Several factors implicated in hypoxia-induced angiogenesis may be involved in IH development. However, the small sample size and retrospective approach of the study preclude definitive conclusions. Prospective studies are needed to conclusively determine which of the factors involved in the (hypoxia) cascade are required for an IH to grow, and could thus be a possible target of drugs for IH treatment.
authors.affiliation: Department of Dermatology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Brussels, Belgium.|Department of Paediatric Surgery, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: S R
authors.initials: SR
authors.lastname: Janmohamed
authors.affiliation: Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Brinkhuizen
authors.affiliation: Department of Paediatrics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: den Hollander
authors.affiliation: Department of Paediatric Surgery, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: G C
authors.initials: GC
authors.lastname: Madern
authors.affiliation: Department of Dermatology, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: P C
authors.initials: PC
authors.lastname: de Laat
authors.affiliation: Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: van Steensel
authors.affiliation: Department of Dermatology, Maasstad Hospital, Rotterdam, the Netherlands.
authors.forename: A P
authors.initials: AP
authors.lastname: Oranje
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology*; D018324:Hemangioma, Capillary / Q000503:physiopathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D009386:Neoplastic Syndromes, Hereditary / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A