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Clinical, histopathological, and molecular features of IDH-wildtype indolent diffuse glioma: comparison with typical glioblastoma

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Abstract

Purpose

IDH-wildtype (IDHwt) diffuse gliomas are treated as glioblastoma, however, some of these may show less aggressive clinical courses. The authors investigated the clinical, histopathological, and molecular characteristics of such IDHwt indolent diffuse gliomas (iDGwt), which have not been well documented in the literature.

Methods

Adult patients with IDHwt gliomas admitted between 2011 and 2020 were surveyed. In this particular study, the clinical indolence was defined mainly as having a small enhancing lesion and a stable period for more than 1 month before surgery. The current WHO diagnostic criteria were adapted for the diagnoses. Gene mutations and copy number changes in 43 representative glioma-associated genes, MGMT promoter methylation status, and survival data were compared with those of The Cancer Genome Atlas reference cohort.

Results

Nine out of 180 surveyed cases (5.0%) fulfilled the present criteria of the iDGwt. Considering the representative regulatory pathways, 8 (88.9%), 4 (44.4%), and 1 (11.1%) case had genetic alterations in the PI3K/MAPK, TP53, and RB pathways, respectively. The frequency of the RB pathway alteration was significantly lower than that in the reference cohort (281 of 362 cases: 77.6%). Two cases (22.2%) showing EGFR amplification met the diagnostic criteria for glioblastoma, and the frequency was significantly lower than that in the reference cohort (412 of 426 cases: 96.7%). The overall survival (median: 37.5 months) in the present series was significantly longer than that in the reference cohort (n = 426, median: 13.9 months).

Conclusions

iDGwt lacked the molecular features of glioblastoma except for the PI3K/MAPK pathway alteration.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by a JSPS KAKENHI grant (number JP19K16823) to Dr. Takahiro Ono. The funding agency did not influence the study design, inclusion criteria, analyses, or interpretation of the data.

Funding

This work was supported by a JSPS KAKENHI Grant (Number JP19K16823) to Dr. Takahiro Ono. The funding agency did not influence the study design, inclusion criteria, analyses, or interpretation of the data.

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Authors and Affiliations

  1. Department of Neurosurgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan

    Hayato Suzuki, Takahiro Ono, Masataka Takahashi & Hiroaki Shimizu

  2. Molecular Medicine Laboratory, Bioscience Education and Research Support Center, Akita University School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan

    Souichi Koyota

  3. Department of Pathology, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan

    Tamotsu Sugai

  4. Department of Surgical Pathology, Akita University Hospital, 44-2 Hasunuma Hiroomote, Akita, Akita, 010-8543, Japan

    Hiroshi Nanjo

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  1. Hayato Suzuki
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  2. Takahiro Ono
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  3. Souichi Koyota
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  4. Masataka Takahashi
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  5. Tamotsu Sugai
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  6. Hiroshi Nanjo
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  7. Hiroaki Shimizu
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Contributions

All authors contributed to the study conception and design. Material preparation and data collection and analysis were performed by HS, TO, SK, MT, TS, and HN. The first draft of the manuscript was written by HS and TO. HS supervised the study. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Takahiro Ono.

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The authors declare no competing interests.

Competing interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The institutional review board of Akita University approved this study (the approval number: 2427).

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Informed consent was obtained from all individual participants included in the study.

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Suzuki, H., Ono, T., Koyota, S. et al. Clinical, histopathological, and molecular features of IDH-wildtype indolent diffuse glioma: comparison with typical glioblastoma. J Neurooncol 159, 397–408 (2022). https://doi.org/10.1007/s11060-022-04074-9

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  • DOI: https://doi.org/10.1007/s11060-022-04074-9

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