title: Absence of IDH1-R132H mutation predicts rapid progression of nonenhancing diffuse glioma in older adults.
abstract: Advanced age and contrast enhancement portend a poor prognosis in diffuse glioma (DG). Diffuse glioma may present as nonenhancing tumors that rapidly progress in weeks to months to a pattern of ring enhancement, characteristic of glioblastoma (GBM). Mutations involving isocitrate dehydrogenase 1 (IDH1) have recently emerged as important diagnostic and prognostic markers in DG. R132H is the most common mutation, expressed in more than 80% of DG and secondary GBM but in less than 10% of primary GBM. Adults older than 50 years with nonenhancing, rapidly progressing DG were identified. A comparison group comprised randomly selected, age-matched patients with nonenhancing, nonprogressing DG. Isocitrate dehydrogenase 1 status was evaluated using anti-IDH1-R132H antibodies (Dianova, Hamburg, Germany). The results were correlated with the clinical outcomes. We identified 4 patients who presented with nonenhancing DG that rapidly progressed to ring-enhancing lesions that were subsequently diagnosed on surgical resection as GBM. This group showed absent IDH1-R132H expression, which is characteristic of primary GBM. The comparison group of 5 patients presented with nonenhancing, nonprogressing DG, and all 5 tumors showed IDH1-R132H expression. In conclusion, negative IDH1-R132H mutation status in nonenhancing DG of older adults is a poor prognostic factor associated with rapid progression to ring-enhancing GBM. The shorter interval of progression and negative IDH1-R132H mutation status suggest a similar molecular pathway as seen in primary GBM.
authors.affiliation: Department of Pathology and Genomic Medicine, The Methodist Hospital, Houston, TX, USA. aolar@tmhs.org
authors.forename: Adriana
authors.initials: A
authors.lastname: Olar
authors.forename: Aditya
authors.initials: A
authors.lastname: Raghunathan
authors.forename: Constance T
authors.initials: CT
authors.lastname: Albarracin
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Aldape
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Cahill
authors.forename: Suzanne Z
authors.initials: SZ
authors.lastname: Powell
authors.forename: J Clay
authors.initials: JC
authors.lastname: Goodman
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Fuller
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human