title: Utility of ATRX immunohistochemistry in diagnosis of adult diffuse gliomas.
abstract: OBJECTIVE
  We performed an immunohistochemical analysis of alpha-thalassaemia/mental retardation syndrome X-linked (ATRX) expression in adult diffuse gliomas, with reference to clinicopathological and genetic features, to determine the utility of this analysis in diagnostic practice.
  
  
  RESULTS
  A total of 193 adult diffuse gliomas underwent immunohistochemical analysis. In areas in which internal controls, neurones, glia and blood vessels were properly stained, the ATRX immunoreactivity of tumour cells was either almost totally absent or completely retained in all cases. There was perfect concordance between the immunohistochemical results and ATRX mutation status, which was known in 19 cases. ATRX loss was observed in 54.5, 30.8 and 0.0% of grades II/III astrocytomas, oligoastrocytomas and oligodendrogliomas, respectively, and 12.7% of glioblastomas. In grades II/III gliomas, most ATRX-loss cases (92.3%) had IDH1/2 mutations. ATRX loss was associated significantly with TP53 mutation and p53 overexpression (P < 0.001), but was never accompanied by 1p/19q co-deletion. IDH1/2 mutation in ATRX-loss tumours was less frequent in glioblastomas than in grades II/III gliomas (P < 0.001). Further, there was no significant association between ATRX loss and p53 overexpression in glioblastomas. ATRX-loss glioblastomas affected younger patients (P < 0.001) and occurred more frequently in locations other than the cerebral hemispheres (P = 0.006). Most grades II/III gliomas (93.3%) were categorized into three molecular subtypes based on the status of IDH1/2 mutation, ATRX immunohistochemistry and 1p/19q co-deletion.
  
  
  CONCLUSIONS
  Distinct histological and molecular characteristics of adult diffuse gliomas with and without ATRX immunoreactivity indicate the utility of ATRX immunohistochemistry in diagnostic practice.
authors.affiliation: Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Ikemura
authors.affiliation: Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Shibahara
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Akitake
authors.initials: A
authors.lastname: Mukasa
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Shunsaku
authors.initials: S
authors.lastname: Takayanagi
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.|Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Aihara
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Saito
authors.affiliation: Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.affiliation: Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000175:diagnosis* / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis* / Q000378:metabolism; D005910:Glioma / Q000175:diagnosis* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009837:Oligodendroglioma / Q000175:diagnosis* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D000075924:X-linked Nuclear Protein; D055815:Young Adult
chemical_list: D009687:Nuclear Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein
keywords: 1p/19q co-deletion; ATRX; IDH 1/2; diffuse glioma; p53