Radiological and Pathological Features Associated with IDH1-R132H Mutation Status and Early Mortality in Newly Diagnosed Anaplastic Astrocytic Tumours

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) mm(2)/sec vs. 0.838 x 10(-3) mm(2)/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 cm(3) in patients with IDH1-R132H-positive tumours while edema ≥ 1 cm beyond the tumour margin and < 5 mitoses/mm(2) 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.