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Loss of H3K27me3 in WHO grade 3 meningioma

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Abstract

Immunohistochemical quantification of H3K27me3 was reported to distinguish meningioma patients with an unfavorable prognosis but is not yet established as a prognostic biomarker within WHO grade 3 meningiomas. We studied H3K27me3 loss in a series of biopsies from primary and secondary malignant meningioma to validate its prognostic performance and describe if loss of H3K27me3 occurs during malignant transformation. Two observers quantified H3K27me3 status as “complete loss”, < 50% and > 50% stained cells in 110 tumor samples from a population-based consecutive cohort of 40 WHO grade 3 meningioma patients. We found no difference in overall survival (OS) in patients with > 50% H3K27me3 retention compared to < 50% in the cohort of patients with WHO grade 3 meningioma (Wald test p = 0.5). H3K27me3 staining showed heterogeneity in full section tumor slides while staining of the Barr body and peri-necrotic cells complicated quantification further. H3K27me3 expression differed without a discernible pattern between biopsies from repeated surgeries of meningioma recurrences. In conclusion, our results were not compatible with a systematic pattern of immunohistochemical H3K27me3 loss being associated with OS or malignant transformation of meningiomas and did not support H3K27me3 loss as a useful immunohistochemical biomarker within grade 3 meningiomas due to staining-specific challenges in quantification.

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Data availability statement

The data presented in this study are available on request from the corresponding author.

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Acknowledgements

The authors thank the Biomedical Laboratory Scientists at the Pathology Department, Rigshospitalet, for their technical expertise and support.

Funding

This research was funded by the Danish Cancer Society, Grant number A16459 and the Lundbeck Foundation.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Copenhagen University Hospital, Rigshospitalet, Inge Lehmanns Vej 6, Copenhagen, Denmark

    Andrea Daniela Maier, Christian Mirian, Jeppe Haslund-Vinding, Jiri Bartek Jr. & Tiit Mathiesen

  2. Pathology Department, Copenhagen University Hospital, Rigshospitalet, Inge Lehmanns Vej 7, Copenhagen, Denmark

    Andrea Daniela Maier, Christian Beltoft Brøchner & David Scheie

  3. Department of Neurosurgery, Karolinska University Hospital, Eugeniavagen 3, Solna, 171 64, Stockholm, Sweden

    Jiri Bartek Jr.

  4. Department of Clinical Neuroscience, Karolinska Institutet, Solnavägen 1, Solna, 171 77, Stockholm, Sweden

    Jiri Bartek Jr. & Tiit Mathiesen

  5. Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden

    Tomas J. Ekström

  6. Department of Molecular Medicine and Surgery, Karolinska Institutet, Solnavägen 1, Solna, 171 77, Stockholm, Sweden

    Tomas J. Ekström

  7. Department of Neurosurgery, Odense University Hospital, Kløvervænget 47, Odense, Denmark

    Frantz Rom Poulsen

  8. Clinical Institute, University of Southern Denmark and BRIDGE, Winsløwparken 19, Odense, Denmark

    Frantz Rom Poulsen

  9. Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, Copenhagen, Denmark

    Tiit Mathiesen

Authors
  1. Andrea Daniela Maier
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  2. Christian Beltoft Brøchner
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Contributions

Conceptualization, ADM, TM, DS and CBB; methodology, ADM, CBB, DS, CM.; software, ADM.; validation, CBB, ADM and DS; formal analysis, ADM and CM.; investigation, ADM and CBB; resources, ADM and DS; data curation, ADM; writing—original draft preparation, ADM, TM, JB, JHV, CM, CBB, TJE, FP and DS; writing—review and editing, ADM, TM, JB, JHV, CM, CBB, DS, TJE, TM, FP and DS; visualization, ADM, CBB.; supervision, TM, DS, FP, TJE; project ad-ministration, ADM; funding acquisition, ADM. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Andrea Daniela Maier.

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The authors declare no conflict of interest.

Institutional review board statement

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Danish Ethics Committee (number H-6–2014-010).

Informed consent statement

Patient consent was waived since the study does not involve any further health risks or cause the patients any further harm and obtaining informed consent was estimated as disproportionately difficult.

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Maier, A.D., Brøchner, C.B., Mirian, C. et al. Loss of H3K27me3 in WHO grade 3 meningioma. Brain Tumor Pathol 39, 200–209 (2022). https://doi.org/10.1007/s10014-022-00436-3

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  • DOI: https://doi.org/10.1007/s10014-022-00436-3

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