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


CONCLUSIONS
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.
Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan. mnatsumeda@bri.niigata-u.ac.jp.
Manabu
M
Natsumeda
Center for Integrated Brain Sciences, Brain Research Institute, University of Niigata, Niigata, Japan. higara@bri.niigata-u.ac.jp.
Hironaka
H
Igarashi
Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan. tnomut@gmail.com.
Toshiharu
T
Nomura
Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan. oguryou@bri.niigata-u.ac.jp.
Ryosuke
R
Ogura
Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan. yoshi.tsukamoto@me.com.
Yoshihiro
Y
Tsukamoto
Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan. tsu-koba@tch.pref.toyama.jp.
Tsutomu
T
Kobayashi
Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan. aoki1123@bri.niigata-u.ac.jp.
Hiroshi
H
Aoki
Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan. oko-okamoto@bri.niigata-u.ac.jp.
Kouichirou
K
Okamoto
Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan. kakita@bri.niigata-u.ac.jp.
Akiyoshi
A
Kakita
Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan. hitoshi@bri.niigata-u.ac.jp.
Hitoshi
H
Takahashi
Center for Integrated Brain Sciences, Brain Research Institute, University of Niigata, Niigata, Japan. tnakada@bri.niigata-u.ac.jp.
Tsutomu
T
Nakada
Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan. yfujii@bri.niigata-u.ac.jp.
Yukihiko
Y
Fujii
D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005910:Glioma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005977:Glutarates / Q000378:metabolism*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D053208:Kaplan-Meier Estimate; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D012680:Sensitivity and Specificity
D005977:Glutarates; C019417:alpha-hydroxyglutarate; D007521:Isocitrate Dehydrogenase