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.
Glioma IDH1 Immunohistochemistry
This is a preview of subscription content, log in to check access.
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.).
Capper D, Zentgraf H, Balss J et al (2009) Monoclonal antibody specific for IDH1 R132H mutation. Acta Neuropathol 118:599–601CrossRefPubMedGoogle Scholar
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 390:547–551PubMedCentralCrossRefPubMedGoogle Scholar
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 28:107–114CrossRefPubMedGoogle Scholar
Wang F, Travins J, DeLaBarre B et al (2013) Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science 340:622–626CrossRefPubMedGoogle Scholar
Schumacher T, Bunse L, Pusch S et al (2014) A vaccine targeting mutant IDH1 induces antitumour immunity. Nature 512:324–327CrossRefPubMedGoogle Scholar
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 31:67–76CrossRefPubMedGoogle Scholar
Hirose T, Nobusawa S, Nakazato Y, Sasaki A (2013) A case of oligodendroglioma with prominent neuronal differentiation. Hum Pathol 44:2353–2359CrossRefPubMedGoogle Scholar
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2007) WHO classification of tumours of the central nervous system. IARC Press, LyonGoogle Scholar
Capper D, Weissert S, Balss J et al (2010) Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol 20:245–254CrossRefPubMedGoogle Scholar
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 32:224–228CrossRefPubMedGoogle Scholar
Kato Y, Natsume A, Kaneko MK (2013) A novel monoclonal antibody GMab-m1 specifically recognizes IDH1-R132G mutation. Biochem Biophys Res Commun 432:564–567CrossRefPubMedGoogle Scholar
Ohgaki H, Dessen P, Jourde B et al (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64(19):6892–6899CrossRefPubMedGoogle Scholar
Watanabe T, Nobusawa S, Kleihues P, Ohgaki H (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174:1149–1153PubMedCentralCrossRefPubMedGoogle Scholar
Kato Y (2014) Specific monoclonal antibodies against IDH1/2 mutations as diagnostic tools for gliomas. Brain Tumor Pathol 32:3–11CrossRefPubMedGoogle Scholar
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 108:361–373CrossRefPubMedGoogle Scholar
Takano S, Tian W, Matsuda M et al (2011) Detection of IDH1 mutation in human gliomas: comparison of immunohistochemistry and sequencing. Brain Tumor Pathol 28:115–123CrossRefPubMedGoogle Scholar