VASCULAR MORPHOLOGY AND ANGIOGENESIS IN GLIAL TUMORS

Intracranial tumor classification is paralleled by a grading system th at empirically compares tumor entities with ''progression stages'' of supratentorial gliomas of the adult. This grading system is an integra l part of the WHO classification. Glioma progression has originally be en defined by descriptive morphology. In this respect, morphological k ey features of high-grade gliomas (WHO grades III and IV) are microvas cular proliferation and the formation of tumor necroses. Glioma progre ssion is now more accurately defined on the molecular genetic level by a stepwise accumulation of oncogene activation and/or tumor suppresso r gene inactivation. Angiogenesis occures during development and progr ession of glial tumors. Pathological vessels are a hallmark of maligna nt glioma and it has therefore been suggested that malignant glioma ce lls are able to induce neovascularization. Despite the exuberant neova scularisation, however, vascular supply may not be sufficient for tumo r areas with high cell proliferation, and necroses may develop. Malign ant transformation of blood vessel itself is a rare event but may be t he underlying mechanism of gliosarcoma development. The recently purif ied vascular endothelial growth factor (VEGF) is at present the only m itogen known to selectively act on endothelial cells. Growing evidence suggests that VEGF is the key regulator of developmental and patholog ical angiogenesis. In vivo, VEGF mRNA is upregulated in a subpopulatio n of malignant glioma cells adjacent to necroses. Since VEGF is hypoxi a-inducible, hypoxia may be an important regulator of VEGF mRNA expres sion and tumor angiogenesis in vivo. Two tyrosine kinase receptors for VEGF are expressed in vessels which invade the tumor, suggesting that tumor angiogenesis is regulated by a paracrine mechanism. The analysi s of mechanisms which regulate tumor and/or hypoxia induced angiogenes is can be of importance for the biology, diagnosis and treatment of bo th ischemic and neoplastic diseases.