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Brain Tumor Pathology

, Volume 32, Issue 3, pp 169–175 | Cite as

Diagnostic advantage of double immunohistochemistry using two mutation-specific anti-IDH antibodies (HMab-1 and MsMab-1) in gliomas

  • Shingo Takano
  • Yukinari Kato
  • Tetsuya Yamamoto
  • Xing Liu
  • Eiichi Ishikawa
  • Mika K. Kaneko
  • Satoshi Ogasawara
  • Masahide Matsuda
  • Masayuki Noguchi
  • Akira Matsumura
Original Article

Abstract

Isocitrate dehydrogenase (IDH) mutation is a valuable prognostic marker and a tool for decision-making for glioma treatment. An algorithm for IDH mutation screening was recently proposed—it consists of a two-step process of an initial search for the most common IDH1-R132H mutation using immunohistochemistry (IHC)-based assay, followed by DNA-based analysis of IHC-negative or -equivocal cases. Here, we report that immunohistochemistry using two mutation-specific anti-IDH monoclonal antibodies (mAbs)—an IDH1-R132H-specific mAb (clone HMab-1) and a multi-specific mAb (clone MsMab-1)—is easy and reliable for IDH mutation screening. We investigated the IDH status of 54 grade III gliomas. For the first screening, we used HMab-1 IHC and for the second, (of HMab-1-negative cases) we used MsMab-1 IHC. The double IHC screening results were confirmed using sequence analysis (100 % specificity and 100 % sensitivity). Thirty of 54 cases (55.6 %) had IDH mutations and the remaining 24 were of the IDH wild type; moreover, the screening results predicted grade III glioma prognosis. IDH sequencing procedures are popular but inconsistent across laboratories. By contrast, double IHC screening using HMab-1 and MsMab-1 is very reliable for detecting IDH1/2 mutations and can predict survival in grade III glioma patients.

Keywords

Glioma IDH Immunohistochemistry Monoclonal antibody Mutation 

Notes

Acknowledgments

We thank Yoshiko Tsukada, Makiko Miyakawa, Takuro Nakamura, Noriko Saidoh, and Kanae Yoshida for their excellent technical assistance. This work was supported in part by Grants-in-Aid for Scientific Research (to S.T., No. 24390339; to Y.K., No. 25462242) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan; by the Platform for Drug Discovery, Informatics, and Structural Life Science from MEXT, Japan (to Y.K.); by the Basic Science and Platform Technology Program for Innovative Biological Medicine from MEXT, Japan (to Y.K.); by the Regional Innovation Strategy Support Program from MEXT, Japan (to Y.K.); by a Health Labour Sciences Research Grant from the Ministry of Health, Labour, and Welfare of Japan (to Y.K.); and by the Japan Brain Foundation (to S.T.) and the Japanese Foundation for Multidisciplinary Treatment of Cancer (to S.T.).

Conflict of interest

The authors declare no conflicts of interest.

Supplementary material

10014_2015_214_MOESM1_ESM.pptx (393 kb)
Supplementary Figure 1. Background staining with MsMab-1. IDH1-R132H case (A, B), IDH wild-type case (C, D). HMab-1 stained nicely IDH1-R132H (A) and revealed no stain against IDH wild type (C) using LSAB2 kit. By contrast, MsMab-1 revealed background staining both against IDH1-R132H (B) and IDH wild type (D) using LSAB2 kit. However, MsMab-1 revealed no background staining against the same case using Envision + kit (see Supplementary Fig. 2F) (PPTX 393 kb)
10014_2015_214_MOESM2_ESM.pptx (690 kb)
Supplementary Figure 2. Comparison between HMab-1 and MsMab-1 against IDH1-R132H. HMab-1 (A, C, E) detected IDH1-R132H more strongly and frequently than MsMab-1 (B, D, F) (PPTX 689 kb)

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Copyright information

© The Japan Society of Brain Tumor Pathology 2015

Authors and Affiliations

  • Shingo Takano
    • 1
  • Yukinari Kato
    • 2
  • Tetsuya Yamamoto
    • 1
  • Xing Liu
    • 2
  • Eiichi Ishikawa
    • 1
  • Mika K. Kaneko
    • 2
  • Satoshi Ogasawara
    • 2
  • Masahide Matsuda
    • 1
  • Masayuki Noguchi
    • 3
  • Akira Matsumura
    • 1
  1. 1.Department of Neurosurgery, Faculty of MedicineUniversity of TsukubaTsukubaJapan
  2. 2.Department of Regional InnovationTohoku University Graduate School of MedicineSendaiJapan
  3. 3.Department of Pathology, Faculty of MedicineUniversity of TsukubaTsukubaJapan

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