title: VEGFR2 expression and TGF-β signaling in initial and recurrent high-grade human glioma.
abstract: OBJECTIVE
  Bevacizumab has promising activity against glioma, although reasons for poor efficacy and variable response rates in certain patients are unclear. Vascular endothelial growth factor receptor 2 (VEGFR2) is heterogeneously expressed within the microvasculature of various malignancies. Moreover, transforming growth factor β (TGF-β), a negative prognostic factor for glioma, is intimately involved in angiogenesis including VEGFR2 regulation. Our objective was to associate expression of VEGFR2 and TGF-β activity with clinicopathological features of human glioma.
  
  
  METHODS
  Expression patterns determined by immunohistochemistry for VEGFR2 and phosphorylated Smad2 in human gliomas were compared to overall survival, progression-free survival (PFS), initial versus recurrent tumors and tumor grade.
  
  
  RESULTS
  Endothelial VEGFR2 expression was low or undetectable in normal tissue but the proportion of VEGFR2-positive vessels increased with tumor grade. Decreased PFS was associated with tumors whose vessels had increased proportions of VEGFR2 at recurrence. Neither parenchymal nor endothelial cell p-Smad2 was associated with tumor grade; however, the former was negatively correlated with overall survival in glioblastoma multiforme.
  
  
  CONCLUSIONS
  The molecular phenotype of the vasculature based on the status of VEGFR2 but not p-Smad2 is related to aspects of glioma progression and patient response. Changes in VEGFR2-positive vessels may account for variable therapeutic efficacy of anti-angiogenic agents.
authors: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ont., Canada.
authors: Elizabeth A
authors: EA
authors: Kuczynski
authors: Steven G
authors: SG
authors: Patten
authors: Brenda L
authors: BL
authors: Coomber
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D012008:Recurrence; D015398:Signal Transduction / Q000502:physiology*; D051899:Smad2 Protein / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis* / Q000502:physiology
chemical_list: C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; D040301:Vascular Endothelial Growth Factor Receptor-2