Skip to main content

Advertisement

SpringerLink
Log in

Evaluation of IDH1 status in diffusely infiltrating gliomas by immunohistochemistry using anti-mutant and wild type IDH1 antibodies

  • Original Article
  • Published:
Brain Tumor Pathology Aims and scope Submit manuscript

Abstract

Glioma cells with the isocitrate dehydrogenase (IDH) 1 G395A mutation are strongly immunopositive for mIDH1R132H, an antibody against mutant IDH1R132H (clone H09). However, we encountered some gliomas which were ambiguously positive for mIDH1R132H despite having the IDH1 G395A mutation. The aim of this study was to establish an evaluation procedure of IDH1 status by immunohistochemistry. Forty-three diffusely infiltrating gliomas were studied, and four of eight anaplastic oligoastrocytomas with the IDH1 G395A mutation were modestly or weakly positive for both the mIDH1R132H and an antibody against wild type IDH1, RcMab-1. Based on our staining results, the IDH1 expression of both wild and mutated types seemed to be codominant and also to be evenly suppressed under a certain condition. We propose a procedure for determining IDH1 status. If a glioma is weakly positive for mIDH1R132H, immunohistochemistry for RcMab-1 should be performed. If the tumor cells are strongly positive for RcMab-1, the IDH1 G395A mutation is judged to be absent on the grounds that IDH1 expression is not suppressed. If the tumor cells are weakly positive for both mIDH1R132H and RcMab-1, then a conclusion should be made after DNA sequencing. This procedure is useful for practical evaluation of IDH1 status.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ichimura K (2012) Molecular pathogenesis of IDH mutations in gliomas. Brain Tumor Pathol 29:131–139

    Article  CAS  PubMed  Google Scholar 

  2. Reitman ZJ, Yan H (2010) Isocitrate dehydrogenase 1 and 2 mutations in cancer: alterations at a crossroads of cellular metabolism. J Natl Cancer Inst 102:932–941

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Dang L, White DW, Gross S et al (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Zhao S, Lin Y, Xu W et al (2009) Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1α. Science 324:261–265

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Noushmehr H, Weisenberger D, Diefes K (2010) Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 17:510–522

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Xu W, Yang H, Liu Y et al (2011) Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell 19:17–30

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Arita H, Narita Y, Yoshida A et al (2015) IDH1/2 mutation detection in gliomas. Brain Tumor Pathol 32:79–89

    Article  CAS  PubMed  Google Scholar 

  8. Capper D, Zentgraf H, Balss J et al (2009) Monoclonal antibody specific for IDH1 R132H mutation. Acta Neuropathol 118:599–601

    Article  CAS  PubMed  Google Scholar 

  9. Kato Y, Jin G, Kuan C-T et al (2009) A monoclonal antibody IMab-1 specifically recognizes IDH1R132H, the most common glioma-derived mutation. Biochem Biophys Res Commun 390:547–551

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Ikota H, Nobusawa S, Tanaka Y et al (2011) High-throughput immunohistochemical profiling of primary brain tumors and non-neoplastic systemic organs with a specific antibody against the mutant isocitrate dehydrogenase 1 R132H protein. Brain Tumor Pathol 28:107–114

    Article  CAS  PubMed  Google Scholar 

  11. Rohle D, Popovici-Muller J, Palaskas N et al (2013) An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science 340:626–630

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Wang F, Travins J, DeLaBarre B et al (2013) Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science 340:622–626

    Article  CAS  PubMed  Google Scholar 

  13. Schumacher T, Bunse L, Pusch S et al (2014) A vaccine targeting mutant IDH1 induces antitumour immunity. Nature 512:324–327

    Article  CAS  PubMed  Google Scholar 

  14. Ishizawa K, Hirose T, Sugiyama K et al (2012) Pathologic diversity of glioneuronal tumor with neuropil-like islands: a histological and immunohistochemical study with a special reference to isocitrate dehydrogenase 1 (IDH1) in 5 cases. Clin Neuropathol 31:67–76

    Article  PubMed  Google Scholar 

  15. Hirose T, Nobusawa S, Nakazato Y, Sasaki A (2013) A case of oligodendroglioma with prominent neuronal differentiation. Hum Pathol 44:2353–2359

    Article  PubMed  Google Scholar 

  16. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2007) WHO classification of tumours of the central nervous system. IARC Press, Lyon

    Google Scholar 

  17. Capper D, Weissert S, Balss J et al (2010) Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol 20:245–254

    Article  CAS  PubMed  Google Scholar 

  18. Kaneko MK, Tsujimoto Y, Hozumi Y et al (2013) Novel monoclonal antibodies GMab-r1 and LMab-1 specifically recognize IDH1-R132G and IDH1-R132L mutations. Monoclon Antib Immunodiagn Immunother 32:224–228

    Article  CAS  PubMed  Google Scholar 

  19. Kato Y, Natsume A, Kaneko MK (2013) A novel monoclonal antibody GMab-m1 specifically recognizes IDH1-R132G mutation. Biochem Biophys Res Commun 432:564–567

    Article  CAS  PubMed  Google Scholar 

  20. Ohgaki H, Dessen P, Jourde B et al (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64(19):6892–6899

    Article  CAS  PubMed  Google Scholar 

  21. Watanabe T, Nobusawa S, Kleihues P, Ohgaki H (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174:1149–1153

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Kato Y (2014) Specific monoclonal antibodies against IDH1/2 mutations as diagnostic tools for gliomas. Brain Tumor Pathol 32:3–11

    Article  PubMed  Google Scholar 

  23. Takano S, Kato Y, Yamamoto T et al (2012) Immunohistochemical detection of IDH1 mutation, p53, and internexin as prognostic factors of glial tumors. J Neurooncol 108:361–373

    Article  CAS  PubMed  Google Scholar 

  24. Takano S, Tian W, Matsuda M et al (2011) Detection of IDH1 mutation in human gliomas: comparison of immunohistochemistry and sequencing. Brain Tumor Pathol 28:115–123

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Mr. Koji Isoda and Mr. Yu Otaki (Gunma University) for their excellent technical assistance. This work was supported in part by Platform for Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Y.K.), and a Grant-in-Aid for Young Scientists (B) (No. 24790346) from the Japan Society for the Promotion of Science (to H.I.).

Conflict of interest

The authors have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Human Pathology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Hayato Ikota, Sumihito Nobusawa & Hideaki Yokoo

  2. Department of Diagnostic Pathology, Gunma University Hospital, Maebashi, Japan

    Hideo Arai

  3. Department of Regional Innovation, Tohoku University Graduate School of Medicine, Sendai, Japan

    Yukinari Kato

  4. Department of Pathology, Saitama Medical University, Saitama, Japan

    Keisuke Ishizawa

  5. Department of Pathology for Regional Communication, Kobe University, Kobe, Japan

    Takanori Hirose

Authors
  1. Hayato Ikota
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sumihito Nobusawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hideo Arai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yukinari Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Keisuke Ishizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takanori Hirose
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hideaki Yokoo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hayato Ikota.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ikota, H., Nobusawa, S., Arai, H. et al. Evaluation of IDH1 status in diffusely infiltrating gliomas by immunohistochemistry using anti-mutant and wild type IDH1 antibodies. Brain Tumor Pathol 32, 237–244 (2015). https://doi.org/10.1007/s10014-015-0222-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10014-015-0222-8

Keywords

Search

Navigation