title: Proliferation and maturation of microvessels in arteriovenous malformations--expression patterns of angiogenic and cell cycle-dependent factors.
abstract: BACKGROUND
  Areas of microvascular proliferation have been observed in a subpopulation of symptomatic congenital vascular malformations later in life. We investigated whether this angiogenic response is followed by a stage of maturation.
  
  
  METHODS
  Resections of vascular malformations (n = 15), infantile hemangiomas (IHs) (n = 8) and pyogenic granulomas (PGs) (n = 5) were studied. Histopathologically, all lesions were screened for presence of foci of immature and/or mature microvessels. These areas were further studied immunohistochemically for differential expression of several angiogenic factors, cell cycle-dependent proteins, p53 and active caspase3. Immunostains were scored semiquantitatively.
  
  
  RESULTS
  Immature microvessel areas were present in five vascular malformations (all of the arteriovenous type), five IHs and five PGs; these lesions also contained transitions between immature and mature microvessels. Conglomerates of mature microvessels were found in 19 cases (6 vascular malformations, 5 PGs and 8 IHs). Expression of vascular endothelial growth factor-A, angiopoietin-1, Ki-67, p16 and p21/27 ratios were overall significantly lower in mature areas than in immature areas including those in vascular malformations. P53 and caspase3 expression was scarce in all lesions.
  
  
  CONCLUSIONS
  Microvascular areas in vascular malformations appear to follow the same pattern of vascular proliferation and maturation as seen in other microvascular lesions of skin and soft tissue.
authors.affiliation: Department of Pathology, Symbiant/Medical Center Alkmaar, Alkmaar, The Netherlands.
authors.forename: Lorine B
authors.initials: LB
authors.lastname: Meijer-Jorna
authors.forename: Chris M
authors.initials: CM
authors.lastname: van der Loos
authors.forename: Peter
authors.initials: P
authors.lastname: Teeling
authors.forename: Onno J
authors.initials: OJ
authors.lastname: de Boer
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Chantal M A M
authors.initials: CM
authors.lastname: van der Horst
authors.forename: Allard C
authors.initials: AC
authors.lastname: van der Wal
mesh_terms: D042683:Angiopoietin-1 / Q000096:biosynthesis*; D001165:Arteriovenous Malformations / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D005260:Female; D017789:Granuloma, Pyogenic / Q000378:metabolism / Q000473:pathology; D006391:Hemangioma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D018797:Cell Cycle Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C505407:CASP3 protein, human; D053148:Caspase 3