THE EXPRESSION OF NITRIC-OXIDE SYNTHASES IN HUMAN BRAIN-TUMORS AND PERITUMORAL AREAS

Nitric oxide, a potent signalling molecule produced from L-arginine by nitric oxide synthase (NOS), has been implicated in diverse pathophys iological processes. Many characteristics of malignant tumours such as increased vascular permeability, vasodilation, neovascularisation and free radical injury to the tumour and adjacent normal tissues are bel ieved to be mediated by nitric oxide. While NOS expression has been de monstrated in brain rumours, no equivalent studies have yet been repor ted on the adjacent peritumoral brain region. The present study examin ed the pattern of NOS expression in the human tumour and peritumoral b rain areas. Biopsies were obtained from eight patients (six gliomas, o ne each of meningioma and metastatic adenocarcinoma) from three areas: tumour, peritumoral, and apparently 'normal' adjacent brain tissue. I mmunohistochemical staining was performed for three isoforms of NOS: b rain NOS (BNOS), endothelial NOS (ENOS) and macrophage-specific NOS (M acNOS). Except for glioblastoma multiforme and metastatic adenocarcino ma, the tumour cells expressed all three NOS isoforms. In four tumours , there was a demonstrable gradient of ENOS expression falling away fr om the tumour. In three gliomas, many glial cells were intensely label led with BNOS. This labelling decreased in the peritumoral tissues. In four tumours, cells (presumably lymphocytes, and CD 45 positive macro phages) were labelled intensely with MacNOS in and around the blood ve ssels. These results suggest that nitric oxide is produced in the tumo ur cells and endothelium of tumour vasculature, while occasionally gli al cells may also be induced to produce it. The possible role of nitri c oxide in the production of peritumoral oedema is discussed. (C) 1998 Elsevier Science B.V.