Neuronal nitric oxide synthase expression in glial tumors: correlation with malignancy and tumor proliferation

Introduction: Increased vascular permeability, vasodilatation, neovascularization and free radical injury in malignant tumors and adjacent normal tissues are believed to be mediated by nitric oxide (NO). High levels of neuronal nitric oxide synthase (nNOS) have been demonstrated in cultured and intracerebral cells. Our aim was to investigate nNOS expression in human glial tumors and to assess its correlation with the histologic grade and proliferative potential. Methods: Tissue specimens were obtained from 29 patients with supratentorial astrocytomas [15 glioblastoma multiforme (GBM), six anaplastic astrocytomas (AA) and eight low grade astrocytomas (LGA)] diagnosed and classified according to the current WHO classification of nervous system tumors. Immunohistochemical staining was performed in paraffin embedded specimens with polyclonal anti-nNOS antibody, and the levels of nNOS expression was evaluated as slight, moderate or dense on the basis of intensity and the extent of distribution of nNOS immunoreactivity. Proliferative potential was evaluated with immunostaining for Ki-67. Results: There was a significant positive correlation between the histologic grade and nNOS expression in terms of intensity and the extent of distribution of nNOS immunoreactivity (p < 0.05). Greater values of Ki-67 indices were demonstrated in tumors with higher nNOS expression, indicating a positive correlation between proliferative potentials and expression of nNOS immunoreactivity. Conclusion: Our study suggests that nNOS expression is increased in glial tumors, which was significantly correlated with histologic grade and proliferative potential. NO overproduction due to overexpression of nNOS activity, seems to have significant correlation with malignancy in glial tumors, and may provide another target for anti-proliferative therapy in the future. [Neurol Res 2008; 30: 940-944]