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Immunohistochemical detection of IDH1 mutation, p53, and internexin as prognostic factors of glial tumors

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Abstract

Isocitrate dehydrogenase 1 (IDH1) mutations, which are early and frequent genetic alterations in astrocytomas, oligodendrogliomas, oligoastrocytomas, and secondary glioblastomas, are specific to arginine 132 (R132). Recently, we established monoclonal antibodies (mAbs) against IDH1 mutations: anti-IDH1-R132H and anti-IDH1-R132S. However, the importance of immunohistochemistry using the combination of those mAbs has not been elucidated. For this study, 164 cases of glioma were evaluated immunohistochemically for IDH1 mutations (R132H and R132S) using anti-IDH1 mAbs (HMab-1 and SMab-1). IDH1 mutation was detected, respectively, in 9.7%, 63.6%, 51.7%, and 77.8% of primary grade IV, secondary grade IV, grade III, and grade II gliomas. For each grade of glioma, prognostic factors for progression-free survival and overall survival were evaluated using clinical and pathological parameters in addition to IDH1 immunohistochemistry. IDH1 mutation, p53 overexpression, and internexin expression, as evaluated using immunohistochemistry with clinical parameters such as degree of surgical removal and preoperative Karnofsky Performance Status (KPS), might be of greater prognostic significance than histological grading alone in grade III as well as IDH1 mutation in grade IV gliomas.

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Acknowledgments

We thank Yoshiko Tsukada, Makiko Miyakawa, Imi Saito, and Junko Aita for their excellent technical assistance. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (S.T., Y.K., M.K.K.), Japan Brain Foundation (S.T.), The Japanese Foundation for research and promotion of endoscopy (S.T.), Japanese Foundation for Multidisciplinary Treatment of Cancer (S.T.), Mitsubishi Pharma Research Foundation (Y.K., M.K.K.), Children Cancer Association of Japan (Y.K.), Intelligent Cosmos Academic Foundation (Y.K.), and Office for Gender Equality of Yamagata University (M.K.K.).

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Authors and Affiliations

  1. Department of Neurological Surgery, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, 305-8575, Ibaraki, Tsukuba, Japan

    Shingo Takano, Tetsuya Yamamoto, Eiichi Ishikawa, Masahide Matsuda, Kei Nakai, Koji Tsuboi & Akira Matsumura

  2. Molecular Tumor Marker Research Team, Yamagata University Global COE Program, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, 990-9585, Yamagata, Japan

    Yukinari Kato, Mika Kato Kaneko, Yuta Tsujimoto, Ryo Yanagiya & Shunpei Morita

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  1. Shingo Takano
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Correspondence to Shingo Takano or Yukinari Kato.

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Shingo Takano and Yukinari Kato contributed equally to this work.

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Takano, S., Kato, Y., Yamamoto, T. et al. Immunohistochemical detection of IDH1 mutation, p53, and internexin as prognostic factors of glial tumors. J Neurooncol 108, 361–373 (2012). https://doi.org/10.1007/s11060-012-0837-0

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  • DOI: https://doi.org/10.1007/s11060-012-0837-0

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