Reliable diagnosis of IDH-mutant glioblastoma by 2-hydroxyglutarate detection: a study by 3-T magnetic resonance spectroscopy

Neurosurg Rev. 2018 Apr;41(2):641-647. doi: 10.1007/s10143-017-0908-y. Epub 2017 Sep 27.

Abstract

We have previously reported that reliable detection of 2-hydroxyglutarate (2HG) in isocitrate dehydrogenase (IDH)-mutant WHO grade 2 and 3 gliomas is possible utilizing 3.0-T single-voxel magnetic resonance spectroscopy (SVMRS). We set out to determine whether the same method could be applied to detect 2HG in IDH-mutant glioblastoma. Forty-four patients harboring glioblastoma underwent pre-operative MRS evaluation to detect 2HG and other metabolites. Presence of IDH-mutations was determined by IDH1 R132H immunohistochemical analysis and DNA sequencing of surgically obtained tissues. Six out of 44 (13.6%) glioblastomas were IDH-mutant. IDH-mutant glioblastoma exhibited significantly higher accumulation of 2HG (median 3.191 vs. 0.000 mM, p < 0.0001, Mann-Whitney test). A cutoff of 2HG = 0.897 mM achieved high sensitivity (100.0%) and specificity (92.59%) in determining IDH-mutation in glioblastoma. Glioblastoma with high 2HG accumulation did not have significantly longer overall survival than glioblastoma with low 2HG accumulation (p = 0.107, log-rank test). Non-invasive and reliable detection of 2HG in IDH-mutant glioblastoma was possible by 3.0-T SVMRS.

Keywords: 2-Hydroxyglutarate; Glioblastoma; IDH mutation; Magnetic resonance spectroscopy.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Child
  • Female
  • Glioblastoma / diagnosis*
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glutarates / metabolism*
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Magnetic Resonance Spectroscopy*
  • Male
  • Middle Aged
  • Mutation / genetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Glutarates
  • alpha-hydroxyglutarate
  • Isocitrate Dehydrogenase