ANGIOGENESIS IN VULVAR INTRAEPITHELIAL NEOPLASIA

Vulvar intraepithelial neoplasia (VIN) has been reported to be a precu rsor of invasive vulvar cancer. Switching to the angiogenic phenotype is considered a key step in tumor growth. Microvessel density (MVD) an d vascular endothelial growth factor (VEGF), a highly angiogenic pepti de, are important parameters of tumor angiogenesis. Forty-three histol ogic slides with 38 VIN I-III lesions were immunohistochemically stain ed for factor VIII-related antigen (F8-RA) and 44 slides with 37 VIN I -III for VEGF, since F8-RA reliably highlights tumor microvessels. Det ermination of MVD and VEGF expression was done by counting microvessel s and VEGF-positive cells at a magnification of 200x and 400x. The hig hest concentration of F8-R4-stained MVD and VEGF expression was found at a small subepithelial area at the border of the VIN lesion to the s troma underneath but concentrations were low in all specimens of norma l epithelium. Nigh VEGF expression was significantly correlated to hig h MVD. For both MVD and VEGF expression the differences between VIN I and VIN III and between VIN II and VIN III were statistically signific ant (P < 0.0001). VIN III lesions are the clinical relevant precursors of invasive cancer of the vulva, as outlined by intense expression of VEGF protein and a highly dense network of microvessels underlying th e dysplastic epithelium. (C) 1997 Academic Press.