Top

Published in:

01-04-2018 | Original Article

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

Authors: Manabu Natsumeda, Kunio Motohashi, Hironaka Igarashi, Takanori Nozawa, Hideaki Abe, Yoshihiro Tsukamoto, Ryosuke Ogura, Masayasu Okada, Tsutomu Kobayashi, Hiroshi Aoki, Hitoshi Takahashi, Akiyoshi Kakita, Kouichirou Okamoto, Tsutomu Nakada, Yukihiko Fujii

Published in: Neurosurgical Review | Issue 2/2018

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.

Parsons DW, Jones C, Zhang X, Cheng-Ho Lin J, Leary RJ, Angenendt P, Mankoo P, Carter H, Sui I, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Nagahashi M, Shinjo SMO, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Volgelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812CrossRefPubMedPubMedCentral

Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, VE V, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773. https://doi.org/10.1056/NEJMoa0808710 CrossRefPubMedPubMedCentral

Polivka J, Polivka J Jr, Rohan V, Pesta M, Repik T, Pitule P, Topolcan O (2014) Isocitrate dehydrogenase-1 mutations as prognostic biomarker in glioblastoma multiforme patients in West Bohemia. Biomed Res Int 2014:735659. https://doi.org/10.1155/2014/735659 CrossRefPubMedPubMedCentral

Ogura R, Tsukamoto Y, Natsumeda M, Isogawa M, Aoki H, Kobayashi T, Yoshida S, Okamoto K, Takahashi H, Fujii Y, Kakita A (2015) Immunohistochemical profiles of IDH1, MGMT and P53: practical significance for prognostication of patients with diffuse gliomas. Neuropathology 35:324–335. https://doi.org/10.1111/neup.12196 CrossRefPubMed

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Ellison DW, Figarella-Branger D, Perry A, Reifenberger G, von Deimling A (2016) WHO classification of tumours of the central nervous system. IARC, Lyon

Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, Ito S, Yang C, Wang P, Xiao MT, Liu LX, Jiang WQ, Liu J, Zhang JY, Wang B, Frye S, Zhang Y, Xu YH, Lei QY, Guan KL, Zhao SM, Xiong Y (2011) Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell 19:17–30. https://doi.org/10.1016/j.ccr.2010.12.014 CrossRefPubMedPubMedCentral

Natsumeda M, Igarashi H, Nomura T, Ogura R, Tsukamoto Y, Kobayashi T, Aoki H, Okamoto K, Kakita A, Takahashi H, Nakada T, Fujii Y (2014) Accumulation of 2-hydroxyglutarate in gliomas correlates with survival: a study by 3.0-tesla magnetic resonance spectroscopy. Acta Neuropathol Commun 7:158. https://doi.org/10.1186/s40478-014-0158-y

Provencher SW (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30:672–679. https://doi.org/10.1002/mrm.1910300604 CrossRefPubMed

Tkac I, Oz G, Adriany G, Ugurbil K, Gruetter R (2009) In vivo 1H NMR spectroscopy of the human brain at high magnetic fields: metabolite quantification at 4T vs. 7T. Magn Reson Med 62:868–879. https://doi.org/10.1002/mrm.22086 CrossRefPubMedPubMedCentral

10.

Takado Y, Igarashi H, Terajima K, Shimohata T, Ozawa T, Okamoto K, Nishizawa M, Nakada T (2011) Brainstem metabolites in multiple system atrophy of cerebellar type: 3.0-T magnetic resonance spectroscopy study. Mov Disord 26:1297–1302. https://doi.org/10.1002/mds.23550 CrossRefPubMed

11.

Pope WB, Prins RM, Albert Thomas M, Nagarajan R, Yen KE, Bittinger MA, Salamon N, Chou AP, Yong WH, Soto H, Wilson N, Driggers E, Jang HG, Su SM, Schenkein DP, Lai A, Cloughesy TF, Kornblum HI, Wu H, Fantin VR, Liau LM (2012) Non-invasive detection of 2-hydroxyglutarate and other metabolites in IDH1 mutant glioma patients using magnetic resonance spectroscopy. J Neuro-Oncol 107:197–205. https://doi.org/10.1007/s11060-011-0737-8 CrossRef

12.

Elkhaled A, Jalbert LE, Phillips JJ, Yoshihara HA, Parvataneni R, Srinivasan R, Bourne G, Berger MS, Chang SM, Cha S, Nelson SJ (2012) Magnetic resonance of 2-hydroxyglutarate in IDH1-mutated low-grade gliomas. Sci Transl Med 4:116ra5 1–116ra510. https://doi.org/10.1126/scitranslmed.3002796 CrossRef

13.

Nagashima H, Tanaka K, Sasayama T, Irino Y, Sato N, Takeuchi Y, Kyotani K, Mukasa A, Mizukawa K, Sakata J, Yamamoto Y, Hosoda K, Itoh T, Sasaki R, Kohmura E (2016) Diagnostic value of glutamate with 2-hydroxyglutarate in magnetic resonance spectroscopy for IDH1 mutant glioma. Neuro-Oncology 18:1559–1568PubMedPubMedCentral

14.

Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC, Marks KM, Prins RM, Ward PS, Yen KE, Liau LM, Rabinowitz JD, Cantley LC, Thompson CB, Vander Heiden MG, Su SM (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744. https://doi.org/10.1038/nature08617 CrossRefPubMedPubMedCentral

15.

Seltzer MJ, Bennett BD, Joshi AD, Gao P, Thomas AG, Ferraris DV, Tsukamoto T, Rojas CJ, Slusher BS, Rabinowitz JD, Dang CV, Riggins GJ (2010) Inhibition of glutaminase preferentially slows growth of glioma cells with mutant IDH1. Cancer Res 70:8981–8987. https://doi.org/10.1158/0008-5472.CAN-10-1666 CrossRefPubMedPubMedCentral

16.

Chaumeil MM, Larson PE, Woods SM, Cai L, Eriksson P, Robinson AE, Lupo JM, Vigneron DB, Nelson SJ, Pieper RO, Phillips JJ, Ronen SM (2014) Hyperpolarized [1-13C] glutamate: a metabolic imaging biomarker of IDH1 mutational status in glioma. Cancer Res 74:4247–4257. https://doi.org/10.1158/0008-5472.CAN-14-0680 CrossRefPubMedPubMedCentral

17.

Crisi G, Orsingher L, Filice S (2013) Lipid and macromolecules quantitation in differentiating glioblastoma from solitary metastasis: a short-echo time single-voxel magnetic resonance spectroscopy study at 3 T. J Comput Assist Tomogr 37:265–271. https://doi.org/10.1097/RCT.0b013e318282d2ba CrossRefPubMed

18.

Choi C, Ganji SK, DeBerardinis RJ, Hatanpaa KJ, Rakheja D, Kovacs Z, Yang XL, Mashimo T, Raisanen JM, Marin-Valencia I, Pascual JM, Madden CJ, Mickey BE, Malloy CR, Bachoo RM, Maher EA (2012) 2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas. Nat Med 18:624–629. https://doi.org/10.1038/nm.2682 CrossRefPubMedPubMedCentral

19.

Choi C, Ganji S, Hulsey K, Madan A, Kovacs Z, Dimitrov I, Zhang S, Pichumani K, Mendelsohn D, Mickey B, Malloy C, Bachoo R, Deberardinis R, Maher E (2013) A comparative study of short- and long-TE (1)H MRS at 3 T for in vivo detection of 2-hydroxyglutarate in brain tumors. NMR Biomed 26:1242–1250. https://doi.org/10.1002/nbm.2943 CrossRefPubMedPubMedCentral

20.

Andronesi OC, Kim GS, Gerstner E, Batchelor T, Tzika AA, Fantin VR, Vander Heiden MG, Sorensen AG (2012) Detection of 2-hydroxyglutarate in IDH-mutated glioma patients by in vivo spectral-editing and 2D correlation magnetic resonance spectroscopy. Sci Transl Med 4:116 ra4 1–116 ra410. https://doi.org/10.1126/scitranslmed.3002693 CrossRef

21.

Esmaeili MVR, Bathen TF (2013) 2-hydroxyglutarate as a magnetic resonance biomarker for glioma subtyping. Transl Oncol 6:92–98. https://doi.org/10.1593/tlo.12424 CrossRefPubMedPubMedCentral

22.

Andronesi OC, Rapalino O, Gerstner E, Chi A, Batchelor TT, Cahill DP, Sorensen AG, Rosen BR (2013) Detection of oncogenic IDH1 mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate. J Clin Invest 123:3659–3663. https://doi.org/10.1172/JCI67229 CrossRefPubMedPubMedCentral

23.

Chaumeil MM, Radoul M, Najac C, Eriksson P, Viswanath P, Blough MD, Chesnelong C, Luchman HA, Cairncross JG, Ronen SM (2016) Hyperpolarized (13)C MR imaging detects no lactate production in mutant IDH1 gliomas: implications for diagnosis and response monitoring. Neuroimage Clin 12:180–189. https://doi.org/10.1016/j.nicl.2016.06.018 CrossRefPubMedPubMedCentral

24.

Hu J, Salzillo TC, Sailasuta N, Lang FF, Bhattacharya P (2017) Interrogating IDH mutation in brain tumor: magnetic resonance and hyperpolarization. Top Magn Reson Imaging 26:27–32. https://doi.org/10.1097/RMR.0000000000000113 PubMedPubMedCentral

25.

Nobusawa S, Watanabe T, Kleihues P, Ohgaki H (2009) IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res 15:6002–6007. https://doi.org/10.1158/1078-0432.CCR-09-0715 CrossRefPubMed

26.

SongTao Q, Lei Y, Si G, YanQing D, HuiXia H, XueLin Z, LanXiao W, Fei Y (2012) IDH mutations predict longer survival and response to temozolomide in secondary glioblastoma. Cancer Sci 103:269–273. https://doi.org/10.1111/j.1349-7006.2011.02134.x CrossRefPubMed

27.

Beiko J, Suki D, Hess KR, Fox BD, Cheung V, Cabral M, Shonka N, Gilbert MR, Sawaya R, Prabhu SS, Weinberg J, Lang FF, Aldape KD, Sulman EP, Rao G, McCutcheon IE, Cahill DP (2014) IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection. Neuro-Oncology 16:81–91. https://doi.org/10.1093/neuonc/not159 CrossRefPubMed

28.

Andronesi OC, Loebel F, Bogner W, Marjanska M, Vander Heiden MG, Iafrate AJ, Dietrich J, Batchelor TT, Gerstner ER, KJW G, Chi AS, Rosen BR, Cahill DP (2016) Treatment response assessment in IDH-mutant glioma patients by non-invasive 3D functional spectroscopic mapping of 2-hydroxyglutarate. Clin Can Res 22:1632–1641CrossRef

Title: Reliable diagnosis of IDH-mutant glioblastoma by 2-hydroxyglutarate detection: a study by 3-T magnetic resonance spectroscopy
Authors: Manabu Natsumeda
Kunio Motohashi
Hironaka Igarashi
Takanori Nozawa
Hideaki Abe
Yoshihiro Tsukamoto
Ryosuke Ogura
Masayasu Okada
Tsutomu Kobayashi
Hiroshi Aoki
Hitoshi Takahashi
Akiyoshi Kakita
Kouichirou Okamoto
Tsutomu Nakada
Yukihiko Fujii
Publication date: 01-04-2018
Publisher: Springer Berlin Heidelberg
Published in: Neurosurgical Review / Issue 2/2018
Print ISSN: 0344-5607
Electronic ISSN: 1437-2320
DOI: https://doi.org/10.1007/s10143-017-0908-y

At a glance: The STEP trials

Springer Medicine

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

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2018

Clinical investigation of chronic subdural hematoma with impending brain herniation on arrival

A population-based study of injuries to the brachial plexus and to the peripheral nerves of the shoulder girdle and upper limb in the Italian region Friuli Venezia Giulia

Pregnancy and delivery in moyamoya vasculopathy: experience of a single European institution

Significance of human chorionic gonadotropin as a predictor of resistance to standard chemo-radiotherapy for pure germinoma

Symptomatic and silent cerebral infarction following surgical clipping of unruptured intracranial aneurysms: incidence, risk factors, and clinical outcome

Prospective and retrospective study of videoconference telemedicine follow-up after elective neurosurgery: results of a pilot program