Microvessel density (MVD) and expression of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), acting as a highly specific inducer of angiogenesis, were evaluated in tissue specimens of 25 patients with squamous cell cancer of the vulva. MVD was quantified by immunostaining for factor VIII-related antigen at one field of 0.25 mm(2). VPF/VEGF expression was evaluated immunohistochemically using a monoclonal anti-VEGF antibody. FIGO stages I, II, and III were diagnosed in 12, 7, and 6 patients, respectively, MVD >20/field was found in 10 of 25 tumors and moderate or strong expression of VPF/VEGF in 10 of 25 tumors, High MVD was significantly more frequent in tumors with moderate or strong VPF/VEGF expression compared to tumors with no or weak VPF/VEGF expression (P = 0.01), Overall survival rates of patients with tumors of high MVD (P = 0.01) and strong VPF/VEGF expression (P < 0.01) were significantly poorer compared to those patients with low MVD or poor VPF/VEGF expression, Strong VPF/VEGF expression and high MVD are considered important parameters of tumor angiogenesis and therefore are related to poor survival probability in vulvar cancer patients. (C) 1996 Academic Press, Inc.