VASCULAR ENDOTHELIAL GROWTH PERMEABILITY FACTOR EXPRESSION IN HUMAN GLIOMA SPECIMENS - CORRELATION WITH VASOGENIC BRAIN EDEMA AND TUMOR-ASSOCIATED CYSTS/

Peritumoral vasogenic brain edema (PVBE) is a common accompaniment of malignant gliomas. It results from microvascular extravasation of plas ma fluid and proteins through the interendothelial spaces. Tumor-assoc iated cysts (TACs) are observed more commonly with benign gliomas that are not associated with PVBE. This study investigates the hypothesis that these morphologically distinct epiphenomena of microvascular extr avasation are linked by a common pathophysiological mechanism involvin g vascular endothelial growth/permeability factor (VEG/PF), which has been implicated in vascular leak phenomena including ascites, malignan t effusions, and brain edema. Furthermore, VEG/PF has been isolated fr om cultured glioma cells, acid both VEG/PF protein and messenger RNA t ranscripts are expressed in brain tumor tissue. To further elucidate t he relationship of VEG/PF to PVBE and TACs, the authors examined 34 pa thological specimens for VEG/PF expression. Nineteen primary low-grade tumors, 11 primary high-grade tumors, and four gliosis controls were immunostained with a polyclonal anti-VEG/PF immunoglobulin C antibody. Magnetic resonance imaging was used to quantitate PVBE and to determi ne the presence of TACs and tumor enhancement. The study revealed that eight VEG/PF-negative specimens exhibited no significant edema, where as 26 VEG/PF-positive tumors exhibited either significant PVBE or TACs . Notably, eight of nine benign TACs that were not associated with PVB E immunostained positive for VEG/PF. These data indicate a high degree of correlation between VEG/PF expression by gliomas and the occurrenc e of PVBE or TACs, irrespective of tumor grade, thus supporting VEG/PF 's pivotal role as the common pathophysiological link between these pr ocesses.