Proliferation and maturation of microvessels in arteriovenous malformations--expression patterns of angiogenic and cell cycle-dependent factors

J Cutan Pathol. 2012 Jun;39(6):610-20. doi: 10.1111/j.1600-0560.2012.01913.x.

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.

MeSH terms

  • Angiopoietin-1 / biosynthesis*
  • Arteriovenous Malformations* / metabolism
  • Arteriovenous Malformations* / pathology
  • Caspase 3 / metabolism
  • Cell Cycle Proteins / biosynthesis*
  • Cell Cycle*
  • Female
  • Granuloma, Pyogenic / metabolism
  • Granuloma, Pyogenic / pathology
  • Hemangioma / metabolism
  • Hemangioma / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • Microvessels* / metabolism
  • Microvessels* / pathology
  • Neovascularization, Pathologic* / metabolism
  • Neovascularization, Pathologic* / pathology
  • Skin* / blood supply
  • Skin* / metabolism
  • Skin* / pathology
  • Tumor Suppressor Protein p53 / metabolism
  • Vascular Endothelial Growth Factor A / biosynthesis*

Substances

  • ANGPT1 protein, human
  • Angiopoietin-1
  • Cell Cycle Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • CASP3 protein, human
  • Caspase 3