title: Radiological and pathological features associated with IDH1-R132H mutation status and early mortality in newly diagnosed anaplastic astrocytic tumours.
abstract: BACKGROUND
  Glioblastoma can occur either de novo or by the transformation of a low grade tumour; the majority of which harbor a mutation in isocitrate dehydrogenase (IDH1). Anaplastic tumours are high-grade gliomas that may represent the final step in the evolution of a secondary glioblastoma or the initial presentation of an early primary glioblastoma. We sought to determine whether pathological and/or radiological variables exist that can reliably distinguish IDH1-R132H-positive from IDH1-R132H-negative tumours and to identify variables associated with early mortality.
  
  
  METHODS
  Patients diagnosed with anaplastic astrocytic tumours were included. Magnetic resonance imaging was performed and immunohistochemistry was used to identify tumours with the IDH1-R132H mutation. Survival was assessed 12 months after diagnosis. Variables associated with IDH1-R132H status were identified by univariate and ROC analysis.
  
  
  RESULTS
  37 gliomas were studied; 18 were positive for the IDH1-R132H mutation. No tumours demonstrated a combined loss of chromosomes 1p/19q. Patients with IDH1-R132H-positive tumours were less likely to die within 12 months of diagnosis (17% vs. 47%; p=0.046), more likely to have tumours located in the frontal lobe (55% vs. 16%; p=0.015), and have a higher minimum apparent diffusion coefficient (1.115 x 10-3 mm2/sec vs. 0.838 x 10-3 mm2/sec; p=0.016), however, these variables demonstrated only moderate strength for predicting the IDH1-R132H mutation status (AUC=0.735 and 0.711, respectively). The Ki-67 index was significantly lower in IDH1-R132H-positive tumours (0.13 vs. 0.21; p=0.034). An increased risk of death was associated with contrast-enhancement ≥ 5 cm3 in patients with IDH1-R132H-positive tumours while edema ≥ 1 cm beyond the tumour margin and < 5 mitoses/mm2 were associated with an increased risk of death in patients with IDH1-R132H-negative tumours.
  
  
  CONCLUSIONS
  IDH1-R132H-positive and -negative anaplastic tumours demonstrate unique features. Factors associated with early mortality are also dependent on IDH1-R132H status and can be used to identify patients at high risk for death.
authors: Division of Laboratory Medicine, Department of Anatomical Pathology, Ottawa, Ontario, Canada; University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors: Jason K
authors: JK
authors: Wasserman
authors: The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada; University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors: Garth
authors: G
authors: Nicholas
authors: Division of Laboratory Medicine, Department of Anatomical Pathology, Ottawa, Ontario, Canada.
authors: Rebecca
authors: R
authors: Yaworski
authors: The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada.
authors: Anne-Marie
authors: AM
authors: Wasserman
authors: Division of Laboratory Medicine, Department of Anatomical Pathology, Ottawa, Ontario, Canada; University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors: John M
authors: JM
authors: Woulfe
authors: Division of Laboratory Medicine, Department of Anatomical Pathology, Ottawa, Ontario, Canada; University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors: Gerard H
authors: GH
authors: Jansen
authors: Division of Neuro-imaging, Department of Medical Imaging, Ottawa, Ontario, Canada; University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors: Santanu
authors: S
authors: Chakraborty
authors: Division of Laboratory Medicine, Department of Anatomical Pathology, Ottawa, Ontario, Canada; University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors: Thanh B
authors: TB
authors: Nguyen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D011379:Prognosis; D011859:Radiography; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human