Correlation of endothelial nitric oxide synthase and vascular endothelial growth factor expression with malignancy in patients with astrocytic tumors

Abstract

Purpose: Many characteristics of malignant brain tumors (increased vascular permeability, vasodilatation, neovascularisation and free radical injury to the tumor and adjacent normal tissues) are believed to be mediated by nitric oxide (NO) synthetized by endothelial NO synthase (eNOS). Overexpression of vascular endothelial growth factor (VEGF) is associated with several central nervous system (CNS) diseases and tumors. Our aim was to study immunohistochemically the coexpression of eNOS and VEGF in astrocytic tumors and to analyse their possible correlation with tumor grade, angiogenesis and proliferation index.

Materials and methods: Sections from 120 randomly selected patients with supratentorial astrocytic tumors [38 glioblastomas (GB), 22 anaplastic astrocytomas (AA) and 20 low-grade astrocytomas (LA)], also including oligodendrogliomas (n=20) and mixed oligoastrocytomas (n=20), were immunostained with monoclonal antibodies for eNOS and VEGF using the avidin-biotin method. The proliferative potential was assessed as the MIB-1 staining index for tumor cells.

Results: There was positive correlation between eNOS and VEGF expressions and histological grade (p<0.05) in terms of intensity and extent of immunoreactivity distribution. Oligodendrogliomas showed significantly less VEGF and eNOS immunoreactivity compared to pure astrocytomas (p<0.05).

Conclusion: Overexpressions of eNOS and VEGF in astrocytic tumors were significantly correlated with histological grade, proliferative potential and malignant transformation. The expression of VEGF in a necrotic and ischemic tumor such as GB is more intense and diffuse than low-grade astrocytomas. These findings suggest that eNOS overexpression in tumor vasculature would be precipitated by transformation into an angiogenic phenotype in the process of neovascularisation in astrocytic tumors.