Accumulation of 2-hydroxyglutarate in gliomas correlates with survival: a study by 3.0-tesla magnetic resonance spectroscopy

Acta Neuropathol Commun. 2014 Nov 7:2:158. doi: 10.1186/s40478-014-0158-y.

Abstract

Introduction: Previous magnetic resonance spectroscopy (MRS) and mass spectroscopy studies have shown accumulation of 2-hydroxyglutarate (2HG) in mutant isocitrate dehydrogenase (IDH) gliomas. IDH mutation is known to be a powerful positive prognostic marker in malignant gliomas. Hence, 2HG accumulation in gliomas was assumed to be a positive prognostic factor in gliomas, but this has not yet been proven. Here, we analyzed 52 patients harboring World Health Organization (WHO) grade II and III gliomas utilizing 3.0-tesla MRS.

Results: Mutant IDH gliomas showed significantly higher accumulation of 2HG (median 5.077 vs. 0.000, p =0.0002, Mann-Whitney test). 2HG was detectable in all mutant IDH gliomas, whereas in 10 out of 27 (37.0%) wild-type IDH gliomas, 2HG was below the detectable range (2HG =0) (p =0.0003, chi-squared test). Screening for IDH mutation by 2HG analysis was highly sensitive (cutoff 2HG =1.489 mM, sensitivity 100.0%, specificity 72.2%). Gliomas with high 2HG accumulation had better overall survival than gliomas with low 2HG accumulation (p =0.0401, Kaplan-Meier analysis).

Discussion: 2HG accumulation detected by 3.0-tesla MRS not only correlates well with IDH status, but also positively correlates with survival in WHO grade II and III gliomas.

MeSH terms

  • Adult
  • Aged
  • Brain / metabolism*
  • Brain / pathology
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Female
  • Glioma / diagnosis
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology
  • Glutarates / metabolism*
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Kaplan-Meier Estimate
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Prognosis
  • Sensitivity and Specificity

Substances

  • Glutarates
  • alpha-hydroxyglutarate
  • Isocitrate Dehydrogenase