title: Combined ATRX/IDH1 immunohistochemistry predicts genotype of oligoastrocytomas.
abstract: OBJECTIVE
  To assess whether in oligoastrocytomas ATRX deficiency, as a surrogate of the alternative lengthening of telomeres (ALT) pathway, has a role in predicting the presence or absence of loss of heterozygosity (LOH) of 1p and 19q, the genetic signature of oligodendroglial differentiation and a favourable prognostic marker.
  
  
  RESULTS
  A series of 54 oligoastrocytomas were investigated by immunohistochemistry as well as microsatellite analysis for LOH 1p19q. Genetic findings were correlated with morphological assessment.
  
  
  CONCLUSIONS
  ATRX deficiency was mutually exclusive with LOH. Conversely, ATRX-proficient tumours immunoreactive for R132H-mutant isocitrate dehydrogenase 1 (IDH1) showed a high rate (85%) of LOH. A more oligodendroglioma-like morphology was associated with a higher rate of LOH even in the morphologically ambiguous group of oligoastrocytomas. Our findings support the concept that oligoastrocytomas represent a morphological grey zone, rather than a group of truly 'mixed' or 'intermediate' tumours. More precise classification of diffuse gliomas may also improve grading of borderline cases. We propose an immunohistochemical algorithm for classification of morphologically ambiguous diffuse gliomas.
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Ekkehard
authors.identifier: http://orcid.org/0000-0002-9128-0364
authors.initials: E
authors.lastname: Hewer
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Istvan
authors.initials: I
authors.lastname: Vajtai
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Matthias S
authors.initials: MS
authors.lastname: Dettmer
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Sabina
authors.initials: S
authors.lastname: Berezowska
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Erik
authors.initials: E
authors.lastname: Vassella
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009837:Oligodendroglioma / Q000145:classification* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059505:Telomere Homeostasis / Q000235:genetics*; D046888:Tissue Array Analysis; D000075924:X-linked Nuclear Protein / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein
keywords: alpha-thalassaemia/mental retardation, X-linked; alternative lengthening of telomeres; isocitrate dehydrogenase 1; oligoastrocytoma