Increased subepithelial vascularization and VEGF expression reveal potentially malignant changes in human oral mucosa lesions

Abstract

The objective of this study was to provide evidence that the magnitude of angiogenesis induced by oral mucosa epithelium with potentially malignant lesions is related to the degree of epithelial aggressiveness. We evaluated 96 biopsies that included: (1) leukoplakia with and without dysplasia, (2) nontumoral borders adjacent to squamous cell carcinomas with and without dysplasia, and (3) normal oral mucosa. Number, size, and localization of vessels labeled immunohistochemically for the antigen CD34 were assessed by image analysis using a software developed "ad hoc." All vascular sections and those localized immediately below the epithelium (sub-basal vessels) were separately evaluated in areas 30-μm deep. Vascular endothelial growth factor (VEGF) expression was labeled immunohistochemically and evaluated semiquantitatively against a standard. Leukoplakia and nontumoral borders adjacent to carcinomas exhibited an increase in VEGF expression and in subepithelial vascularization. This increase was significantly greater in leukoplakia with dysplastic changes than in leukoplakia without dysplasia. Conversely, no differences were observed between epithelia with and without dysplasia adjacent to carcinomas. Demonstration of expression of epithelial VEGF and sub-basal vascularization could be an additional aid for evaluation of the severity of potentially malignant lesions in oral mucosa routine biopsies.