title: EZH2 expression is a prognostic factor in childhood intracranial ependymoma: a Canadian Pediatric Brain Tumor Consortium study.
abstract: BACKGROUND
  The cure rate for childhood intracranial ependymoma is approximately 70% in the setting of a gross total resection followed by radiation, but management remains challenging in patients with residual disease. Therefore, robust biomarkers are needed to guide the development of new targeted therapy. The authors evaluated the expression of several biomarkers in pediatric intracranial ependymoma and observed that the expression of enhancer of zeste homolog 2 (EZH2), a polycomb complex protein involved in epigenetic regulation of gene expression, was independently associated with poor survival.
  
  
  METHODS
  Tissue microarray immunostaining was performed on 180 ependymoma samples from 12 of 16 Canadian pediatric centers. Expression levels of EZH2, Ki-67, B lymphoma Moloney-murine leukemia virus insertion region 1 homolog, tumor protein 16 (P16), Y-box binding protein 1, phosphorylated protein kinase B (pAKT), and epidermal growth factor receptor were evaluated. Cox regression analyses were performed, and the Kaplan-Meier method was used to construct survival curves.
  
  
  RESULTS
  EZH2 expressed in 16% of tumors was associated with inferior 5-year overall survival. Ki-67 and pAKT levels were associated with a poor outcome in patients with posterior fossa ependymoma, and the absence of P16 was associated with a poor outcome in patients with supratentorial ependymoma. Multivariate analysis revealed that younger age and EZH2 expression (95% confidence interval, 1.1-36.0) were independent markers of a poor prognosis.
  
  
  CONCLUSIONS
  EZH2 is a novel, independent marker of a poor prognosis in patients with ependymoma, especially in those who have tumors located in the posterior fossa. EZH2, pAKT, and P16 are potential therapeutic targets, particularly for patients who have tumors in which standard gross total resection plus fractionated radiotherapy is not feasible.
authors.affiliation: Pediatric Hematology/Oncology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Li
authors.forename: Christopher
authors.initials: C
authors.lastname: Dunham
authors.forename: Uri
authors.initials: U
authors.lastname: Tabori
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Carret
authors.forename: P Daniel
authors.initials: PD
authors.lastname: McNeely
authors.forename: Donna
authors.initials: D
authors.lastname: Johnston
authors.forename: Lucie
authors.initials: L
authors.lastname: Lafay-Cousin
authors.forename: Beverly
authors.initials: B
authors.lastname: Wilson
authors.forename: David D
authors.initials: DD
authors.lastname: Eisenstat
authors.forename: Nada
authors.initials: N
authors.lastname: Jabado
authors.forename: Shayna
authors.initials: S
authors.lastname: Zelcer
authors.forename: Mariana
authors.initials: M
authors.lastname: Silva
authors.forename: Katrin
authors.initials: K
authors.lastname: Scheinemann
authors.forename: Christopher
authors.initials: C
authors.lastname: Fryer
authors.forename: Glenda
authors.initials: G
authors.lastname: Hendson
authors.forename: Abbas
authors.initials: A
authors.lastname: Fotovati
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hawkins
authors.forename: Stephen
authors.initials: S
authors.lastname: Yip
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Dunn
authors.forename: Juliette
authors.initials: J
authors.lastname: Hukin
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D000071221:Enhancer of Zeste Homolog 2 Protein; D004806:Ependymoma / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
keywords: AKT; EZH2; brain; childhood; enhancer of zeste homolog 2; ependymoma; protein kinase B