title: Prognostic stratification of patients with anaplastic gliomas according to genetic profile.
abstract: BACKGROUND
  There is a need to improve the current, controversial, and poorly reproducible classification of anaplastic gliomas, which represent a highly heterogeneous entity in terms of survival.
  
  
  METHODS
  The impact of the most common genetic alterations on survival was investigated based on 156 anaplastic gliomas: Among the patients who were included, the gender ratio was 1.32, the median age was 45.5 years (range, 20-83 years), and the median Karnofsky performance status was 70 (range, 40-100). Genetic analysis included a search for loss of heterozygosity (LOH) on chromosomes 1p and 19q; amplification of chromosomes 9p and 10q and of the epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4) and mouse double-minute (MDM2) genes; and p53 expression.
  
  
  RESULTS
  The median survival was 33.5 months, and the median progression-free survival was 15.8 months. In a univariate analysis, LOH on 1p and 19q was correlated with longer survival, whereas p53 expression, LOH on 9p, LOH on 10q, amplified EGFR, and deleted CDKN2A were correlated with shorter survival. LOH on 1p and 19q were associated with oligodendrogliomas, LOH on 10q was related to EGFR amplification, and LOH on 1p and 19q was mutually exclusive with EGFR amplification and LOH on 10q. In a multivariate analysis, the significant prognostic factors were age, histology, LOH on 1p and 19q, and P16/CDKN2A deletion. Recursive partitioning analysis (RPA) divided the whole group hierarchically into 3 distinct prognostic subgroups: Group A with 1p19q codeletion (median survival, 98 months), Group B with EGFR amplification (median survival, 17 months), and Group CC (median survival, 31 months), providing a basis for a genetically based prognostic subclassification for patients with Grade III gliomas.
  
  
  CONCLUSIONS
  The search for 1p19q codeletion and EGFR receptor amplification provides a simple, clinically relevant prognostic subclassification of grade III gliomas.
authors.affiliation: INSERM U711, Biologie des Interactions Neurones et Glie, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Dehais
authors.forename: Florence
authors.initials: F
authors.lastname: Laigle-Donadey
authors.forename: Yannick
authors.initials: Y
authors.lastname: Marie
authors.forename: Michele
authors.initials: M
authors.lastname: Kujas
authors.forename: Julie
authors.initials: J
authors.lastname: Lejeune
authors.forename: Alexandra
authors.initials: A
authors.lastname: Benouaich-Amiel
authors.forename: Marta
authors.initials: M
authors.lastname: Pedretti
authors.forename: Marc
authors.initials: M
authors.lastname: Polivka
authors.forename: Khe-Hoang
authors.initials: KH
authors.lastname: Xuan
authors.forename: Joelle
authors.initials: J
authors.lastname: Thillet
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Delattre
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality; D002878:Chromosomes, Human, Pair 1; D002879:Chromosomes, Human, Pair 10; D002899:Chromosomes, Human, Pair 9; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000401:mortality; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D011379:Prognosis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors