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




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Acta Neuropathologica Communications

, 2:158

First Online: 07 November 2014Received: 22 August 2014Accepted: 22 October 2014

Abstract

IntroductionPrevious 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.

ResultsMutant 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.

Discussion2HG 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.

KeywordsGlioma MRS 2-hydroxyglutarate IDH mutation Prognostic marker Abbreviations2HG2-hydroxyglutarate

2-HGDH2-hydroxyglutarate dehydrogenase

3 T3 tesla

α-ketoglutarateα-KG

ChoCholine

COSY2D correlation spectroscopy

CrCreatine

DNADeoxyribonucleic acid

GABAγ- aminobutyric acid

GlnGlutamine, Glu, glutamate

GlxGlutamine and glutamate

GPCGlycerophosphocholine

GSHGluthathione

IDHIsocitrate dehydrogenase

IHCImmunohistochemistry

InsMyo-inositol

MRIMagnetic resonance imaging

MRSMagnetic resonance spectroscopy

NAAN-acetylaspartate

NAAGN-acetylaspartylglutamate

PCPhosphocholine

PCrPhosphocreatine

PRESSPoint-resolved spectroscopic sequence

ROCReceiver operating characteristic

ROSReactive oxygen species

SDStandard of deviation

S-RSignal-to-noise ratio

SVMRSSingle voxel MRS

TCGAThe Cancer Genome Atlas

tChoTotal choline, tCr, total creatine

TETTen-eleven translocation

tNAATotal NAA

VLBVolume-localized basis

VOIVolume of interest

WHOWorld Health Organization

Electronic supplementary materialThe online version of this article doi:10.1186-s40478-014-0158-y contains supplementary material, which is available to authorized users.

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Fuente: https://link.springer.com/



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