title: Histopathologic assessment of hot-spot microvessel density and vascular patterns in glioblastoma: Poor observer agreement limits clinical utility as prognostic factors: a translational research project of the European Organization for Research and Treatment of Cancer Brain Tumor Group.
abstract: BACKGROUND
  Hot-spot microvessel density (MVD) and vascular patterns have been reported as histopathologic factors that influence prognosis in retrospective series of malignant gliomas. To investigate clinical utility, the authors systematically studied observer agreement on MVD and vascular patterns and the influence of repeatedly assessed data on patient outcomes in 2 independent glioblastoma series.
  
  
  METHODS
  MVD and vascular patterns were assessed retrospectively by 5 observers in 1) a retrospectively compiled glioblastoma series that included 110 patients and 2) a glioblastoma series that included 233 patients who were treated within a randomized trial. MVD was determined in the field of greatest density ("hot-spot"). Predominantly classic or bizarre vascular patterns were determined by using a previously defined algorithm.
  
  
  RESULTS
  Observer agreement on MVD was highly variable (range of kappa values, 0.464-0.901). The worst observer agreement was achieved when both the selection of hot-spots and MVD counts were performed independently. Survival analysis did not show a consistent association between repeatedly assessed MVD and patient outcome. Observer agreement on vascular patterns was poor (kappa = 0.297). Survival analysis did not show a consistent association between repeatedly assessed vascular patterns and patient outcome.
  
  
  CONCLUSIONS
  Observer agreement on hot-spot MVD and vascular patterns in patients with glioblastoma was poor in independent assessments. MVD and vascular patterns were not associated consistently with patient outcome. Based on these findings, the authors concluded that poor observer agreement limits the clinical utility of histopathologically assessed hot-spot MVD and vascular patterns as prognostic factors in patients with glioblastoma. Improved methodologies for morphologic assessment of glioblastoma vascularization need to be identified.
authors.affiliation: Institute of Neurology, Medical University Vienna, Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
authors.forename: Harald
authors.initials: H
authors.lastname: Heinzl
authors.forename: Ellen
authors.initials: E
authors.lastname: Gelpi
authors.forename: Katharina
authors.initials: K
authors.lastname: Schonegger
authors.forename: Christine
authors.initials: C
authors.lastname: Haberler
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
authors.forename: Christine
authors.initials: C
authors.lastname: Marosi
authors.forename: Monika
authors.initials: M
authors.lastname: Hegi
authors.forename: Thierry
authors.initials: T
authors.lastname: Gorlia
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Hainfellner
mesh_terms: D015331:Cohort Studies; D003951:Diagnostic Errors / Q000706:statistics & numerical data*; D005060:Europe; D005909:Glioblastoma / Q000098:blood supply* / Q000175:diagnosis*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data*; D008833:Microcirculation / Q000473:pathology; D015588:Observer Variation; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012955:Societies, Medical; D016019:Survival Analysis