Nitric oxide synthase expression of oligodendrogliomas

In the central nervous system, nitric oxide (NO) has a variety of biological functions including vasorelaxation and neurotransmission. The synthesis of NO is catalyzed by NO synthases (NOS) existing in 3 isoforms, neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). NO synthase has implications in the pathophysiology of primary glial brain tumors with enhanced expression of nNOS and eNOS in high-grade astrocytic tumors, WHO grades III and IV. Only minor groups of pure oligodendrogliomas have been investigated. The aim of the investigation was to study the expression of the 3 NOS isoforms in this genetically divergent group of primary gliomas and to correlate the findings with tumor grade and expression pattern for the major group of gliomas--the astrocytomas. We examined the NOS expression in 35 oligodendrogliomas, WHO grade II, and 7 anaplastic oligodendrogliomas, WHO grade III, by immunohistochemical methods using formalin-fixed paraffin-embedded material. We observed only a minor expression of nNOS and sparse expression of eNOS in the tumor cells, but a vivid expression of eNOS in the vascular endothelial cells in both the tumor and the surrounding tissue. The rich expression of eNOS in oligodendroglioma vessels independent of tumor grade may suggest that blood flow and angiogenesis in these richly vascularized tumors are modified by NO. Interestingly, enhanced expression of inducible NOS was observed in the oligodendroglial tumor cells in 19 of 35 oligodendrogliomas (54%) and in 2 of 7 anaplastic oligodendrogliomas (29%). This is diverging for iNOS expression in astroglial tumors and the data could be indicative of iNOS exerting anti-tumor activity which may protract the progression from low-grade oligodendrogliomas to more anaplastic types.