Endothelial nitric oxide synthase expression in tumor vasculature is correlated with malignancy in human supratentorial astrocytic tumors

OBJECTIVE: Endothelial nitric oxide synthase (eNOS) may play an important r ole in the regulation of tumor blood flow and vascular permeability. Howeve r, there have been no reports describing alterations of eNOS expression in relation to malignant progression in human astrocytic tumors. We immunohist ochemically studied the relationship between eNOS expression in tumor vascu lature and malignancy in supratentorial astrocytic tumors. METHODS: Tissue samples were obtained from 12 patients with low-grade astro cytomas, 10 with anaplastic astrocytomas, and 17 with glioblastomas. Normal brain tissue samples were obtained from four patients with other brain dis eases. Immunohistochemical staining was performed using the avidin-biotin c omplex method, with polyclonal anti-eNOS antibody, and the levels of eNOS e xpression in endothelial cells were evaluated as slight moderate, or intens e on the basis of eNOS immunoreactivity. The proliferative potential was as sessed as the MIB-1 staining index for tumor cells. RESULTS: The expression of eNOS was slight in all specimens of normal brain tissue, slight in 7 and moderate in 5 specimens of low-grade astrocytoma, slight in 2, moderate in 6, and intense in 2 specimens of anaplastic astroc ytoma, and moderate in 5 and intense in 12 specimens of glioblastoma. The M IB-1 staining index (mean +/- standard deviation) was 0.2 +/- 0.2% for norm al specimens, 1.8 +/- 0.6% for low-grade astrocytomas, 9.6 +/- 6.9% for ana plastic astrocytomas, and 18.5 +/- 7.7% for glioblastomas. The MIB-1 staini ng indices for slight, moderate, and intense eNOS expression were 2.0 +/- 2 .3%, 10.8 +/- 9.8%, and 16.9 +/- 7.7%, respectively. CONCLUSION: Expression of eNOS in tumor vessels was significantly correlate d with histological grade and proliferative potential. These findings sugge st that astrocytic tumor vessels possess higher activity for nitric oxide p roduction than do normal vessels.