Vascular endothelial growth/permeability factor expression in human glioma specimens: correlation with vasogenic brain edema and tumor-associated cysts

Abstract

Peritumoral vasogenic brain edema (PVBE) is a common accompaniment of malignant gliomas. It results from microvascular extravasation of plasma fluid and proteins through the interendothelial spaces. Tumor-associated 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 extravasation are linked by a common pathophysiological mechanism involving vascular endothelial growth/permeability factor (VEG/PF), which has been implicated in vascular leak phenomena including ascites, malignant effusions, and brain edema. Furthermore, VEG/PF has been isolated from cultured glioma cells, and both VEG/PF protein and messenger RNA transcripts are expressed in brain tumor tissue. To further elucidate the relationship of VEG/PF to PVBE and TACs, the authors examined 34 pathological 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 G antibody. Magnetic resonance imaging was used to quantitate PVBE and to determine the presence of TACs and tumor enhancement. The study revealed that eight VEG/PF-negative specimens exhibited no significant edema, whereas 26 VEG/PF-positive tumors exhibited either significant PVBE or TACs. Notably, eight of nine benign TACs that were not associated with PVBE immunostained positive for VEG/PF. These data indicate a high degree of correlation between VEG/PF expression by gliomas and the occurrence of PVBE or TACs, irrespective of tumor grade, thus supporting VEG/PF's pivotal role as the common pathophysiological link between these processes.

Immunoexpression of vascular endothelial growth factor in periapical granulomas, radicular cysts, and residual radicular cysts

“…The epithelial expression of VEGF in RCs and RRCs might constitute an additional mechanism for the enlargement of these lesions, maintaining the stimulus for angiogenesis and vascular permeability, a role also proposed by Leonardi et al 18 Results from studies of the expression of VEGF in brain tumor cysts 13,15,17 and cyst fluid of thyroid nodules 14,16 also corroborate this suggestion. According to Vaquero et al, 15 VEGF might enhance accumulation of cyst fluid, together with an increase in oxygen supply boosting the development of the cyst.…”

“…6,18 Therefore, VEGF has been implicated as an important factor in granulation tissue development 7,8,11,12 and cyst enlargement. [13][14][15][16][17] In the present study, we evaluated the expression of VEGF in PGs, RCs, and RRCs. The results revealed that VEGF is expressed in the connective tissue of all of these lesions and in the epithelial lining of RCs and RRCs, corroborating earlier studies.…”

“…It has been speculated that the presence of VEGF in cystic lesions is capable of increasing vascular permeability, leading to accumulation of cystic fluid. [13][14][15][16][17] Leonardi et al 18 proposed a similar function for VEGF in periapical lesions. According to those authors, the expression of VEGF in PGs and RCs has bioactivity to increase vascular permeability, being at a Doctoral student.…”

Blockage of angiotensin II type I receptor decreases the synthesis of growth factors and induces apoptosis in C6 cultured cells and C6 rat glioma

“…Malignant gliomas are still associated with poor prognosis, the mean survival time of patients with glioblastoma multiforme (GBM) is 1 year, and it has not changed significantly for the last three decades (Lopez-Gonzalez and Sotelo, 2000). Glioblastoma multiforme is accompanied by extensive angiogenesis which is essential for tumoral growth and invasiveness; it also produces a vast amount of growth factors such as PDGF, VEGF, HGF and FGF (Strugar et al, 1995;Arrieta et al, 1998Arrieta et al, , 2002Moriyama et al, 1999;Schmidt et al, 1999). In brain parenchyma there is a local RAAS, some neurons, glial cells and glioma cells express renin, angiotensinogen and receptors for Ang II (AT 1 and AT 2 ) (Ganong, 1984, Ariza et al, 1988Fogarty et al, 2002;Juillerat-Jeanneret et al, 2004).…”

Expression of AT1 and AT2 angiotensin receptors in astrocytomas is associated with poor prognosis

“…Despite multidisciplinary therapeutic approaches, the median survival for patients with GM is approximately 12 months after diagnosis (Lopez-Gonzalez and Sotelo, 2000;Sotelo et al, 2006). High-grade astrocytomas (AA and GM) display high cellular proliferation and extensive angiogenesis (Tuettenberg et al, 2006) stimulated by the production of growth factors such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (Strugar et al, 1995;Moriyama et al, 1999;Schmidt et al, 1999;Arrieta et al, 2002). Angiotensin II (ANGII) is the main effector in the renin-angiotensin-aldosterone system (RAAS) -a powerful vasoconstrictor system - (Matsusaka and Ichikawa, 1997) and acts on two membrane-bound receptors (AT1 and AT2).…”