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Primary Orthotopic Glioma Xenografts Recapitulate Infiltrative Growth and Isocitrate Dehydrogenase I Mutation
Published on: January 14, 2014
Less Invasive Phenotype Found in Isocitrate Dehydrogenase-mutated Glioblastomas than in Isocitrate Dehydrogenase
Stephen J Price1, Kieren Allinson1, Hongxiang Liu1
1From the Cambridge Brain Tumour Imaging Laboratory, Division of Neurosurgery (S.J.P., N.R.B., J.L.Y., T.J.L.), and Wolfson Brain Imaging Centre, Department of Clinical Neurosciences (S.J.P., N.R.B., V.C.L., T.J.L.), University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, England; and Department of Histopathology (H.L.) and Molecular Malignancy Laboratory (K.A., H.L.), Addenbrooke's Hospital, Cambridge, England.
Abstract:
Purpose To explore the diffusion-tensor (DT) imaging-defined invasive phenotypes of both isocitrate dehydrogenase (IDH-1)-mutated and IDH-1 wild-type glioblastomas. Materials and Methods Seventy patients with glioblastoma were prospectively recruited and imaged preoperatively. All patients provided signed consent, and the local research ethics committee approved the study. Patients underwent surgical resection, and tumor samples underwent immunohistochemistry for IDH-1 R132H mutations. DT imaging data were coregistered to the anatomic magnetic resonance study and reconstructed to provide the anisotropic and isotropic components of the DT. The invasive phenotype was determined by using previously published criteria and correlated with IDH-1 mutation status by using the Freeman-Halton extension of the Fisher exact probability test. Results Nine patients had an IDH-1 mutation and 61 had IDH-1 wild type. All of the patients with IDH-1 mutation had a minimally invasive DT imaging phenotype. Among the IDH-1 wild-type tumors, 42 of 61 (69%) were diffusively invasive glioblastomas, 14 of 61 (23%) were locally invasive, and five of 61 (8%) were minimally invasive (P < .001). Conclusion IDH-mutated glioblastomas have a less invasive phenotype compared with IDH wild type. This finding may have implications for individualizing the extent of surgical resection and radiation therapy volumes.

