Expression of type 2 nitric oxide synthase and vascular endothelial growth factor in oral dysplasia

Abstract

Purpose: The small molecule nitric oxide (NO), produced by a family of enzymes called NO synthase (NOS), has a diverse array of functions in both physiologic and pathologic states. Prolonged production of NO by the isoform NOS2 has been implicated in human cancer progression. NO has an important role in angiogenesis, being both an upstream signal and a downstream effector molecule to vascular endothelial growth factor (VEGF). The latter group of proteins are crucial for vascular endothelial cell proliferation and permeability. The expression of VEGF increases with cancer progression. Because angiogenesis is a prerequisite for the development of invasive cancer, this immunohistochemical study investigated the expression of NOS2 and VEGF in oral epithelial dysplasia. Materials and Methods: An immunohistochemical study was performed using monoclonal antibodies to NOS2 and VEGF on archival formalin-fixed, paraffin-embedded tissue of 33 cases of oral dysplasia. Results: A significant correlation was found between NOS2 and VEGF expression in oral dysplasia (P <.001). Expression of both NOS2 and VEGF also correlated with the severity of dysplasia (P <.001, P <.002). Conclusions: These findings may provide further understanding to the complex transformation of oral epithelial dysplasia to invasive carcinoma and the role of angiogenesis in this process. © 2002 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 60:1455-1460, 2002