title: IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas.
abstract: BACKGROUND
  Epigenetic, genetic, and molecular studies have identified several diagnostic and prognostic markers in diffuse gliomas. Their importance for evaluating WHO grade II gliomas has yet to be specifically delineated.
  
  
  METHODS
  We analyzed markers, including IDH mutation(IDHmut), 1p19q codeletion(1p19qcodel), ATRX expression loss(ATRX loss) and p53 overexpression, and outcomes in 159 patients with WHO grade II oligodendroglioma, oligoastrocytoma, and astrocytoma (2003-2012).
  
  
  RESULTS
  IDHmut was found in 141(91%) and ATRX loss in 64(87%) of IDHmut-noncodel tumors (p = 0.003). All codeleted tumors (n = 66) were IDHmut. Four subgroups were identified: IDHmut-codel, 66(43%); IDHmut-noncodel-ATRX loss, 60(39%); IDHmut-noncodel-ATRXwt, 9(6%); IDHwt, 14(9%). Median survival among 4 groups was significantly different (p = 0.038), particularly in IDHmut-codel (median survival 15.6 years) compared to the remaining 3 groups (p = 0.025). Survival by histology was not significant. Overall (OS), but not progression-free (PFS), survival was significantly longer with gross total resection vs. biopsy only (p = 0.042). Outcomes for patients with subtotal resection were not significantly different from those with biopsy only. Among these uniformly treated patients, OS far exceeds PFS, particularly in those with 1p/19q codeletion.
  
  
  CONCLUSIONS
  For WHO grade II diffuse glioma, molecular classification using 1p/19qcodel, IDHmut, and ATRX loss more accurately predicts outcome and should be incorporated in the neuropathologic evaluation.
authors.affiliation: Neuro-Oncology, Advocate Medical Group, Park Ridge, IL 60068, USA.
authors.forename: Heather E
authors.initials: HE
authors.lastname: Leeper
authors.affiliation: Experimental Pathology, Mayo Clinic SW, Rochester, MN 55905, USA.
authors.forename: Alissa A
authors.initials: AA
authors.lastname: Caron
authors.affiliation: Biomedical Statistics and Informatics, Mayo Clinic SW, Rochester, MN 55905, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Decker
authors.affiliation: Anatomic Pathology, Mayo Clinic SW, Rochester, MN 55905, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.affiliation: Neurology, Mayo Clinic SW, Rochester, MN 55905, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Lachance
authors.affiliation: Anatomic Pathology, Mayo Clinic SW, Rochester, MN 55905, USA.
authors.forename: Caterina
authors.initials: C
authors.lastname: Giannini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000172:deficiency* / Q000235:genetics*; D001706:Biopsy; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D004265:DNA Helicases / Q000172:deficiency*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D005910:Glioma / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009687:Nuclear Proteins / Q000172:deficiency*; D010641:Phenotype; D012042:Registries; D012189:Retrospective Studies; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D000075924:X-linked Nuclear Protein; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D007521:Isocitrate Dehydrogenase; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein
keywords: 1p19q codeletion; ATRX; IDH mutation; WHO grade II; diffuse gliomas