title: Brain edema in meningiomas is associated with increased vascular endothelial growth factor expression.
abstract: OBJECTIVE
  Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), an endothelial cell-specific cytokine, induces proliferation of endothelial cells and increases vascular permeability dramatically. All gliomas secrete significant amounts of VEGF, whereas meningiomas are variable in expression. Thus, we sought to determine whether the extent of VPF/VEGF expression in meningiomas correlated with differences in brain edema associated with these tumors.
  
  
  METHODS
  Meningioma tissue samples from 37 patients (15 men, average age 65 +/- 13 yr; 22 women, average age 60 +/- 10 yr) who underwent surgery at or were referred to the University of Alabama Hospital were examined retrospectively for the extent of expression of immunoreactive VPF/VEGF. Additionally, peritumoral edema was assessed on a blinded basis radiographically from preoperative magnetic resonance imaging scans. Selected specimens were examined by in situ hybridization to document the source of VPF/VEGF.
  
  
  RESULTS
  The predominant meningioma subclassifications were transitional (57%) or meningothelial (27%) subtypes. VPF/VEGF immunoreactivity ranged from 0 to 3.5, with a median value of 2 on a subjective 5-point scale; magnetic resonance imaging-assessed edema ranged in extent from 0 to 4 (subjective 5-point scale), with a median value of 2.5. The correlation of determination (R2) of magnetic resonance imaging-assessed tumor edema rating and VPF/VEGF staining intensity rating was 0.6087 (r = 0.78; P = 0.0001). In situ hybridization localized VPF/VEGF messenger ribonucleic acid in meningioma cells and not in normal parenchymal brain cells.
  
  
  CONCLUSIONS
  These data suggest that meningioma-associated edema may be a result of the capacity of meningioma cells to produce VPF/VEGF locally, leading to increased tumor neovascularization and enhanced vascular permeability.
authors.affiliation: Brain Tumor Research Laboratories, University of Alabama School of Medicine, Birmingham, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Goldman
authors.forename: S
authors.initials: S
authors.lastname: Bharara
authors.forename: C A
authors.initials: CA
authors.lastname: Palmer
authors.forename: J
authors.initials: J
authors.lastname: Vitek
authors.forename: J C
authors.initials: JC
authors.lastname: Tsai
authors.forename: H L
authors.initials: HL
authors.lastname: Weiss
authors.forename: G Y
authors.initials: GY
authors.lastname: Gillespie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000098:blood supply / Q000473:pathology; D001929:Brain Edema / Q000473:pathology*; D002199:Capillary Permeability / Q000502:physiology; D016228:Endothelial Growth Factors / Q000032:analysis*; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000032:analysis*; D008297:Male; D008577:Meningeal Neoplasms / Q000098:blood supply / Q000473:pathology*; D008579:Meningioma / Q000098:blood supply / Q000473:pathology*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors