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

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 (n=8) and pyogenic granulomas (n=5) were studied. Histopathologically, all lesions were screened for the 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 5 vascular malformations (all of the arteriovenous type), 5 infantile hemangiomas and 5 pyogenic granulomas; these lesions also contained transitions between immature and mature microvessels. Conglomerates of mature microvessels were found in 19 cases (6 vascular malformations, 5 pyogenic granulomas and 8 infantile hemangiomas). Expression of VEGF-A, angiopoietin-1, Ki67, 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. LorineMeyerJorna27-3-12.indd 64 27-3-2012 10:40:42 65 5 Microvascular proliferation and maturation in arteriovenous malformations