VEGF expression in skin warts. Relevance to angiogenesis and vasodilation

Verrucae vulgaris (skin warts) are benign proliferative lesions which are generally associated with human papillomavirus type 2 (HPV-2) infection. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen able to induce angiogenesis and vasodilation. Our previous findings indicate that these two processes take place during the formation of skin warts. The purpose of this study was to determine whether VEGF expression in these lesions was associated with HPV infection, angiogenesis or vasodilation. To this end, paraffin-embedded specimens of skin warts which were either negative for HPV-1, -2, -3 and -4 (HPV-; n = 18), or positive for HPV-2 (HPV+; n = 21) were compared with histologically normal perilesional skin (n = 13). Serial sections were stained with antibodies to von Willebrand Factor (vWF) and to VEGF. Vascularity was quantified by point counting vWF-positive blood vessels. Small and large vessels were quantified separately, using a cut-off value of 50 microm diameter. VEGF expression in the epidermis was estimated by consensus of two independent observers according to three indices: (1) percentage of cells stained, (2) intensity of the staining, and (3) product of area and intensity (final score). Results were analysed by nonparametric tests. Similar levels of VEGF were found in specimens of normal skin, HPV- and HPV+ warts, irrespective of the index used. There was no significant correlation between VEGF expression and vascularity values for either small or large vessels. These results indicate that, on its own, VEGF expression is not associated with angiogenesis, vasodilation or HPV infection in skin warts. The presence of VEGF in normal skin suggests that it may play a role in tissue homeostasis.