title: Microvascularization and expression of VEGF and its receptors in recurring meningiomas: pathobiological data in favor of anti-angiogenic therapy approaches.
abstract: OBJECTIVE
  We studied expression of molecules of the vascular endothelial growth factor (VEGF) pathway and its relation to vascularization, cell proliferation and patient outcome in recurring non-anaplastic meningioma. We studied 29 tumor specimens of 8 patients with recurring meningiomas and of 8 age- and gender-matched control patients with non-recurring meningiomas (including meningothelial, transitional, fibroblastic and atypical subtypes) using immunohistochemistry and in-situ hybridization.
  
  
  RESULTS
  VEGF protein, VEGF-mRNA, VEGF receptor (VEGFR)-1 mRNA, VEGFR-2 mRNA and hypoxia-inducible factor (HIF)-1-α protein were expressed in 27/29 (93%), 20/27 (74%), 9/27 (33.3%), 12/27 (44.4%) and 5/29 (17.2%) specimens, respectively. VEGFR- 2 mRNA expression was found in 6/8 tumors extracted at first operation in patients with recurring tumors and in none of the control cases (p = 0.007). Microvessel density (MVD) and Ki-67 index values were generally higher in meningiomas with expression of angiogenic factors. The association of high Ki-67 index values with VEGF-mRNA expression was significant (p = 0.04). Time to recurrence was shorter in patients with high MVD than in patients with low MVD (p = 0.027).
  
  
  CONCLUSIONS
  High MVD correlates with unfavorable prognosis in our series of recurring meningioma. VEGF and its receptors are frequently expressed in meningiomas and seem important for tumor growth and recurrence. Thus, anti-VEGF therapy in aggressive meningioma seems rational from a pathobiological point of view.
authors.affiliation: Institute of Neurology, Medical University Vienna, Austria. matthias.preusser@meduniwien.ac.at
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
authors.forename: Marco
authors.initials: M
authors.lastname: Hassler
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
authors.forename: Margaretha
authors.initials: M
authors.lastname: Rudas
authors.forename: Till
authors.initials: T
authors.lastname: Acker
authors.forename: Karl H
authors.initials: KH
authors.lastname: Plate
authors.forename: Georg
authors.initials: G
authors.lastname: Widhalm
authors.forename: Engelbert
authors.initials: E
authors.lastname: Knosp
authors.forename: Helene
authors.initials: H
authors.lastname: Breitschopf
authors.forename: Johannes
authors.initials: J
authors.lastname: Berger
authors.forename: Christine
authors.initials: C
authors.lastname: Marosi
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008579:Meningioma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis / Q000096:biosynthesis*; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor