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The utility of DNA methylation analysis in elderly patients with pilocytic astrocytoma morphology

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Abstract

Purpose

Pilocytic astrocytoma (PA) is a circumscribed low-grade astrocytic glioma, generally considered to be associated with a good prognosis. However, a subset of PA patients shows unfavorable outcomes. In this study, we retrospectively reviewed PA patients and performed further molecular analysis, such as DNA methylation profiling, to identify prognostic factors.

Methods

We analyzed 29 histologically-confirmed PA patients from a single center from 2002 to 2021 and conducted integrated molecular analyses among elderly PA patients since age was an independent prognostic factor for poor outcomes.

Results

The median age at diagnosis was 14 years (range 3–82 years) and 4 patients (14%) were elderly (patients ≥ 60 years old). Age over 60 was associated with poor progression-free survival and overall survival. We performed DNA methylation analysis on 2 of the 4 elderly patients. Both cases were histologically diagnosed as PA, but DNA methylation profiling revealed one as high-grade astrocytoma with piloid features (all methylation class scores were below 0.3 in both v11b4 and v12.5) and the other as glioblastoma, IDH-wildtype (score was over 0.5 in both v11b4 and v12.5), using the German Cancer Research Center methylation profiling classifiers and t-SNE analysis.

Conclusions

Elderly patients with PA morphology showed unfavorable outcomes in this cohort. In those patients, further molecular analysis and DNA methylation profiling revealed the possibility of high-grade astrocytic tumors, including newly defined entities.

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Data availability

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

Abbreviations

PA:

Pilocytic astrocytoma

MC AAP:

Methylation-class anaplastic astrocytoma with piloid features

HGAP:

High-grade astrocytoma with piloid features

GTR:

Gross total resection

STR:

Subtotal resection

PR:

Partial resection

PFS:

Progression-free survival

OS:

Overall survival

HE:

Hematoxylin and eosin

IHC:

Immunohistochemistry

t-SNE:

T-distributed stochastic neighbor embedding

KPS:

Karnofsky Performance Score

NF1:

Neurofibromatosis 1

SEER:

Surveillance Epidemiology and End Results

AA:

Anaplastic astrocytoma

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Funding

This study was supported by grants-in-aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology to Y.O. (No.21K20803 and 22K16687) and K.S. (No.22K06951) and the National Cancer Center Rare Cancer Grant (Award Number G007, AY).

Author information

Author notes

  1. Yasuki Suruga and Kaishi Satomi have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurological Surgery, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, kita-ku, Okayama, 700-8558, Japan

    Yasuki Suruga, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Atsuhito Uneda, Nobushige Tsuboi, Keigo Makino, Shuichiro Hirano, Naoya Kemmotsu, Ryoji Imoto, Ryo Mizuta, Takao Yasuhara & Isao Date

  2. Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Kaishi Satomi & Akihiko Yoshida

  3. Department of Pathology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan

    Kaishi Satomi

  4. Department of Neurosurgery and Neuroendovascular Surgery, Hiroshima City Hiroshima Citizens Hospital, 7-33 Moto-machi, Naka-ku, Hiroshima, 730-8518, Japan

    Yusuke Tomita

  5. Department of Pediatrics, Okayama University Hospital, 2-5-1 Shikata-cho, kita-ku, Okayama, 700-8558, Japan

    Kana Washio

  6. Department of Pathology, Okayama University Hospital, 2-5-1 Shikata-cho, kita-ku, Okayama, 700-8558, Japan

    Hiroyuki Yanai

  7. Department of Brain Disease Translational Research, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Yuko Matsushita, Yuko Hibiya & Koichi Ichimura

  8. Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universitat Berlin and Humboldt-Universitat Zu Berlin, Charitéplatz 1, 10117, Berlin, Germany

    David Capper

  9. Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Yoshihiro Otani

Authors
  1. Yasuki Suruga
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  2. Kaishi Satomi
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  3. Yoshihiro Otani
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  4. Kentaro Fujii
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Contributions

Conception and design: YS, KS, YO, KI. Development of the methodology and acquisition of experimental data: YS, KS, YO, YM, YH, KI. Collection of clinical samples and data: YS, YO, KF, JI, AU, NT, KM, SH, NK, RI, RM, YT, TY, KW, HY. Writing, review, and/or revision of the manuscript: YS, KS, YO, KI. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yoshihiro Otani.

Ethics declarations

Competing interests

DC declares that he holds a patent on a method for DNA methylation based tumor classification. The other authors declare that they have no competing interests.

Ethical approval

All procedures in involving human participants were performed in accordance with the ethical standards of the institutional research committee (IRB#1911–023).

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Written consent for participation and publication was obtained.

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Suruga, Y., Satomi, K., Otani, Y. et al. The utility of DNA methylation analysis in elderly patients with pilocytic astrocytoma morphology. J Neurooncol 160, 179–189 (2022). https://doi.org/10.1007/s11060-022-04131-3

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