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Reliability of IDH1-R132H and ATRX and/or p53 immunohistochemistry for molecular subclassification of Grade 2/3 gliomas

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Abstract

Since the World Health Organization 2016 classification (2016 WHO), genetic status has been incorporated into the diagnosis of Grade 2/3 gliomas (lower-grade gliomas). Therefore, immunohistochemistry (IHC) of IDH1-R132H, ATRX, and p53 have been used in place of genetic status. We report the associations between histological findings, IHC, and genetic status. We performed IHC of IDH1-R132H, ATRX, and p53 in 76 lower-grade gliomas and discussed its validity based on the 2016 WHO and the upcoming 2021 WHO classification. The sensitivity and specificity of anti-ATRX, p53, and IDH1-R132H IHC were 40.9%/98.1%, 78.6%/85.4%, and 90.5%/84.6%, respectively. Among 21 IDH1-mutant gliomas without 1p/19q codeletion, two gliomas (9.5%) mimicked the so-called classic for oligodendroglioma (CFO) in their morphology. Of the 42 gliomas with 1p/19q codeletion, four cases were difficult to diagnose as oligodendroglioma through morphological examination. Moreover, there were three confusing cases with ATRX mutations but with retained ATRX-IHC positivity. The lessons learned from this study are as follows: (1) ATRX-IHC and p53-IHC should be supplementary to morphological diagnosis, (2) rare IDH mutations other than IDH1 R132H should be considered, and (3) there is no complete alternative test to detect molecular features of glioblastoma under the 2021 WHO classification.

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Acknowledgements

This research was supported by a Grant-in-Aid for Scientific Research on Innovative Areas “Chemistry for Multimolecular Crowding Biosystems” (A.N.) (JSPS KAKENHI Grant No. 17928985). This research was also supported in part by the Japan Agency for Medical Research and Development (AMED) under Grant Number: JP21am0101078 (to Y.K.).

Funding

Japan Society for the Promotion of Science,17928985,Atsushi Natsume,Japan Agency for Medical Research and Development,JP21am0101078,Yukinari Kato

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Author notes

  1. Tomohide Nishikawa and Reiko Watanabe authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Nagoya University School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan

    Tomohide Nishikawa, Yotaro Kitano, Akane Yamamichi, Kazuya Motomura, Fumiharu Ohka, Kosuke Aoki, Masaki Hirano, Akira Kato, Junya Yamaguchi, Sachi Maeda, Yuji Kibe, Ryuta Saito, Toshihiko Wakabayashi & Atsushi Natsume

  2. Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

    Reiko Watanabe

  3. Department of Neurosurgery, Mie University School of Medicine, Tsu, Mie, Japan

    Yotaro Kitano

  4. Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Yukinari Kato

  5. Department of Pathology, Nagano Red Cross Hospital, 5-22-1 Wakasato, Nagano, Nagano, 380-8582, Japan

    Shuta Sato, Tomoyoshi Ogino & Ichiro Ito

Authors
  1. Tomohide Nishikawa
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  2. Reiko Watanabe
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  4. Akane Yamamichi
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  5. Kazuya Motomura
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  6. Fumiharu Ohka
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  7. Kosuke Aoki
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  8. Masaki Hirano
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  9. Akira Kato
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  15. Yukinari Kato
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  16. Shuta Sato
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  18. Atsushi Natsume
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Contributions

Conceptualization: A.N., R.W. and I.I.; Methodology: A.N., A.Y., K.M., Y. Kitano, R.W., and I.I.; Conduct of Immunohistochemistry: S.S. and T.O.; Formal analysis and investigation: Y. Kitano, A.Y. S.M., Y.K., A.K., R.S., T. W., R.W., and I.I.; Writing-original draft preparation: T.N., R.W., and I.I.; Writing-review and editing: R.W., I.I., and A.N.; Funding acquisition: A.N. and Y. Kato; Resources: Y.M., F.O., K.A., M.M., J.Y., Y. Kitano and Y. Kato; Supervision: A.N. and I.I.

Corresponding authors

Correspondence to Reiko Watanabe, Atsushi Natsume or Ichiro Ito.

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Nishikawa, T., Watanabe, R., Kitano, Y. et al. Reliability of IDH1-R132H and ATRX and/or p53 immunohistochemistry for molecular subclassification of Grade 2/3 gliomas. Brain Tumor Pathol 39, 14–24 (2022). https://doi.org/10.1007/s10014-021-00418-x

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  • DOI: https://doi.org/10.1007/s10014-021-00418-x

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