The HIF-2alpha/VEGF pathway activation in cutaneous capillary haemangiomas.
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.
Giatromanolaki
Alexandra
A
Department of Pathology, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr
Arvanitidou
Vasiliki
V
Hatzimichael
Athanasios
A
Simopoulos
Constantinos
C
Sivridis
Efthimios
E
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
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