title: Expression of vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2 in primary and recurrent WHO grade III meningiomas.
abstract: WHO grade III meningiomas are malignant neoplasms for which new and more targeted treatment strategies are urgently needed. Although clinical trials investigating anti-angiogenic vascular endothelial growth factor (VEGF) targeted therapies are currently recruiting, knowledge about the expression of VEGF and VEGF receptors remains to be determined.
  
  
  
  We investigated the expression of VEGF and its receptors VEGFR1 and VEGFR2 in 32 WHO grade III meningioma samples by immunohistochemistry. Furthermore, we performed in-situ hybridisation for VEGF.
  
  
  
  We found low VEGF expression in tumor and endothelial cells. Highest VEGF expression levels were seen in peri-necrotic tumor cells potentially suffering from hypoxia. VEGFR1 and 2 were virtually absent on tumor cells, although endothelial cells displayed significantly higher levels reaching stronger expression for VEGFR2 than VEGFR1.
  
  
  
  Our findings showing constant expression levels of VEGFR2 in endothelial cells serve as a first indication that the use of small tyrosine kinase inhibitors such as Sunitinib directly targeting the VEGF-receptors might be worth testing, also in the clinical context in cases of therapy-refractory meningiomas. Further investigations are needed to study the response to drugs targeting the VEGF pathway in relation to the expression profile of VEGF and its receptors in high grade meningiomas.
authors.affiliation: Institute of Neurology, Edinger Institute, Goethe University, Frankfurt, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Baumgarten
authors.forename: Benjamin
authors.initials: B
authors.lastname: Brokinkel
authors.forename: Jenny
authors.initials: J
authors.lastname: Zinke
authors.forename: Cornelia
authors.initials: C
authors.lastname: Zachskorn
authors.forename: Heinrich
authors.initials: H
authors.lastname: Ebel
authors.forename: Friedrich K
authors.initials: FK
authors.lastname: Albert
authors.forename: Walter
authors.initials: W
authors.lastname: Stummer
authors.forename: Karl H
authors.initials: KH
authors.lastname: Plate
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Harter
authors.forename: Martin
authors.initials: M
authors.lastname: Hasselblatt
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008579:Meningioma / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077210:Sunitinib