title: Ki67 index in intracranial ependymoma: a promising histopathological candidate biomarker.
abstract: OBJECTIVE
  The Ki67 tumour cell proliferation index is an independent prognostic factor in ependymoma patients. Essential prerequisites for validation of the Ki67 index as a histopathological biomarker are the reproducibility of this factor and its prognostic influence by different observers (proof of objective clinical and analytical performance). To this end, the aim was to analyse systematically inter- and intraobserver agreement and reproducibility of the prognostic impact of the Ki67 index in intracranial ependymoma.
  
  
  RESULTS
  The study cohort contained 78 cases of intracranial ependymoma. In all cases, the Ki67 index was assessed by four experienced observers (EOs) and by four inexperienced observers (IOs) using the manual hot-spot method. There was considerable agreement on Ki67 index assessment. There was higher observer agreement among EOs compared with IOs. For each observer, survival analysis showed significant association of low Ki67 index with favourable patient outcome.
  
  
  CONCLUSIONS
  Our data show that the Ki67 index in intracranial ependymoma is a reproducible and robust prognostic factor and can be considered a promising histopathological candidate biomarker. Attainment of biomarker status requires further translational studies in the context of prospective therapeutic trials.
authors.affiliation: Institute of Neurology, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Preusser
authors.forename: H
authors.initials: H
authors.lastname: Heinzl
authors.forename: E
authors.initials: E
authors.lastname: Gelpi
authors.forename: R
authors.initials: R
authors.lastname: Höftberger
authors.forename: I
authors.initials: I
authors.lastname: Fischer
authors.forename: I
authors.initials: I
authors.lastname: Pipp
authors.forename: I
authors.initials: I
authors.lastname: Milenkovic
authors.forename: A
authors.initials: A
authors.lastname: Wöhrer
authors.forename: F
authors.initials: F
authors.lastname: Popovici
authors.forename: S
authors.initials: S
authors.lastname: Wolfsberger
authors.forename: J A
authors.initials: JA
authors.lastname: Hainfellner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology*; D002452:Cell Count; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D004806:Ependymoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D019394:Ki-67 Antigen / Q000032:analysis*; D008875:Middle Aged; D015588:Observer Variation; D011379:Prognosis; D015203:Reproducibility of Results; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen