title: Magnetic resonance imaging characteristics predict epidermal growth factor receptor amplification status in glioblastoma.
abstract: OBJECTIVE
  Two clinical-molecular glioblastoma subtypes have been described: "primary" glioblastomas arise de novo in older patients and often overexpress epidermal growth factor receptor (EGFR); "secondary" glioblastomas progress from lower-grade tumors in younger patients and commonly have TP53 mutations. EGFR overexpression correlates in experimental gliomas with increased angiogenesis, edema, and invasion. No radiographic predictors of molecular glioblastoma subtype are known.
  
  
  METHODS
  We retrospectively reviewed 75 glioblastomas, classified as TP53-mutated (n=11), EGFR-amplified (n=31), or neither (non-TP53/non-EGFR; n=33). Four variables were derived from preoperative magnetic resonance imaging: (a) T2/T1, the ratio of T2-bright volume to enclosed T1-enhancing volume; (b) percentage of tumor volume that was necrosis; and (c and d) T1 and T2 border sharpness coefficients (BSC), the rates of change in grayscale intensity of adjacent 0.02-cm2 voxels traversing the anterior, posterior, and lateral borders on T1-enhanced and T2 images.
  
  
  CONCLUSIONS
  Mean T2/T1 was 4.7 for EGFR-amplified glioblastomas, greater than that of TP53-mutated glioblastomas (2.3) or non-TP53/non-EGFR glioblastomas (2.6; P<0.00005). All four tumors with T2/T1>7.2 were EGFR-amplified; 0 of 15 with T2/T1<4.7 underwent gross total resection. The mean T2 BSC of EGFR-amplified glioblastomas was 33.7, less sharp (P<0.0000005) than TP53-mutated (72.2) and non-TP53/non-EGFR glioblastomas (81.2). All 15 glioblastomas with T2 BSC<30.8 were EGFR-amplified. Percentage necrosis and T1 BSC did not differ between glioblastoma subtypes. The increased T2/T1 ratio and decreased T2 BSC in EGFR-overexpressing tumors are the first radiographic distinctions described between glioblastoma molecular subtypes. These findings may reflect increased angiogenesis, edema, and/or invasion in EGFR-overexpressing tumors.
authors.affiliation: Neurosurgical Service, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA. maghi@partners.org
authors.forename: Manish
authors.initials: M
authors.lastname: Aghi
authors.forename: Paola
authors.initials: P
authors.lastname: Gaviani
authors.forename: John W
authors.initials: JW
authors.lastname: Henson
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Batchelor
authors.forename: David N
authors.initials: DN
authors.lastname: Louis
authors.forename: Fred G
authors.initials: FG
authors.lastname: Barker
mesh_terms: D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D066246:ErbB Receptors / Q000235:genetics*; D005784:Gene Amplification; D016158:Genes, p53 / Q000235:genetics; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D009154:Mutation; D009336:Necrosis / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; D066246:ErbB Receptors