The relationship between peritumoral brain edema and the expression of vascular endothelial growth factor and its receptors in intracranial meningiomas

Abstract

We examined the radiological and histological features of, and the influences of the expression of VEGF and its two major receptors, Flt-1 and Flk-1, on the development of peritumoral brain edema (PTBE) in patients with intracranial meningiomas. The expressions of VEGF and VEGF receptors in the immunohistochemical study were analyzed in relation to several factors, including tumor size, location, vascularity, and blood supply, as seen on digital subtraction angiographic studies. The edema volume (P = 0.0003) and edema index (P < 0.0001) had a significantly positive relation to VEGF expression. The positivity of Flt-1 and Flk-1 was mainly observed in tumor vessels; 44 cases (37.2%) were positive for the Flt-1 antibody and 37 cases (31.4%) for the Flk-1 antibody. The mean value of the edema index of the positive-Flt-1 group (5.220 +/- 11.586) was significantly higher than that of the negative-Flt-1 group (1.782 +/- 2.559) (P < 0.0001). The mean value of the edema index of the positive-Flk-1 group (3.925 +/- 5.870) was slightly higher than that of the negative-Flk-1 group (2.671 +/- 8.136) (P < 0.0001). Our data suggest that the expressions of VEGF and VEGF receptors positively relate to each other and to the formation of PTBE in patients with meningiomas.

Edema following Gamma Knife radiosurgery for parasagittal and parafalcine meningiomas

“…2,13,18 Patients with significant mass effect and edema associated with a meningioma frequently undergo resection, but this resection may be subtotal in nature. Those meningioma patients selected for SRS may in fact be less likely to exhibit peritumoral edema than those who undergo resection.…”

“…VEGF receptors have also been shown to exhibit a significantly positive relationship to edema volume. 18,29 Combining these factors, some patients with a parafalcine or parasagittal meningioma may experience a period of worsening cerebral edema and accompanying neurological dysfunction following SRS.…”

“…7,17,18,21 Peritumoral edema associated with parasagittal or parafalcine meningiomas is common, with some series showing edema in 48% of patients. 17 At times, the edema may be symptomatic and necessitate medical therapy such as steroids to lessen or relieve symptoms.…”

Expression of aquaporin-4 in human supratentorial meningiomas with peritumoral brain edema and correlation of VEGF with edema formation

“…All patients had three-dimensional MRIs with contrast enhancement and were divided into two groups depending on edema index (EI) (see below) as follows: edema group (EI >1) and non-edema group (EI = 1) (Bitzer et al, 1998;Otsuka et al, 2004). The patients who suffered from other diseases that can cause brain edema or had preoperative steroid therapy were excluded.…”

“…Approximately 60% of patients with meningiomas have PTBE, which can increase the mass effect of the tumor, aggravate clinical symptoms, raise intracranial pressure, and as a result lead to cerebral herniation (Bitzer et al, 1997a,b). Vascular endothelial growth factor (VEGF) has the ability to induce angiogenesis and increase vascular permeability, which is an important factor in the formation of PTBE in meningiomas (Kalkanis et al, 1996;Goldman et al, 1997;Provias et al, 1997;Bitzer et al, 1998;Machein and Plate, 2000;Otsuka et al, 2004;Ding et al, 2008).…”