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Oncogene-induced senescence in meningiomas—an immunohistochemical study

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Abstract

Purpose

Meningiomas are tumours originating from meningothelial cells, the majority belonging to grade 1 according to the World Health Organization classification of the tumours of the Central Nervous System. Factors contributing to the progression to the higher grades (grades 2 and 3) have not been elucidated yet. Senescence has been proposed as a potential mechanism constraining the malignant transformation of tumours. Senescence-associated beta-galactosidase (SA-β-GAL) and inhibitors of cyclin-dependent kinases p16 and p21 have been suggested as senescence markers.

Methods

We analysed 318 meningiomas of total 343 (178 grade 1, 133 grade 2 and 7 grade 3). Tissue microarrays were constructed and stained immunohistochemically, using antibodies for SA-β-GAL, p16 and p21.

Results

The positive correlation of the tumour grade with the expression of p16 (p = 0.016) and SA-β-GAL (p = 0.002) was observed. The expression of p16 and SA-β-GAL was significantly higher in meningiomas grade 2 compared to meningiomas grade 1 (p = 0.006 and p = 0.004, respectively). SA-β-GAL positivity positively correlated with p16 and p21 in the whole cohort. In grade 2 meningiomas, a positive correlation was only between SA-β-GAL and p16. Correlations of senescence markers in meningiomas grade 2 were not present.

Conclusion

Our findings suggest the senescence activation in meningiomas grade 2 as a potential mechanism for the restraining of tumour growth and give hope for applying of promising senolytic therapy.

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Data availability

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

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Department for Pathology, Pathohistology and Medical Cytology, University Clinical Centre of Serbia, Belgrade, Serbia

    Vladimir Mijajlović & Savo Raičević

  2. Department of Cytology, Institute for Biological Research “Siniša Stanković“- National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia

    Marko Miler

  3. Clinic for Neurosurgery, University Clinical Centre of Serbia, Belgrade, Serbia

    Rosanda Ilić

  4. Clinic for Ophthalmology, University Clinical Centre of Serbia, Belgrade, Serbia

    Dejan Rašić

  5. Institute of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Duško Dunđerović & Emilija Manojlović-Gačić

  6. Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Ivan Soldatović

  7. Institute for Pathophysiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Silvio De Luka

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  1. Vladimir Mijajlović
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Contributions

All authors contributed to the study conception and design. VM: acquisition of paraffin blocks and clinical data, construction of tissue micro-array, analysis and interpretation of data, writing the first draft of the paper. MM: interpretation of data, critical review of the paper for important intellectual content. RI: acquisition of clinical data, interpretation of data. DR: diagnosing meningiomas, interpretation of data. DD: construction of tissue micro-array. SR: diagnosing meningiomas, interpretation of data. IS: statistical analysis, interpretation of data. SL: critical review of the paper for important intellectual content. EM: primary idea and composition of the study, construction of tissue micro-array, diagnosing meningiomas, interpretation of data, writing the final version of the paper.

Corresponding author

Correspondence to Emilija Manojlović-Gačić.

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Competing interests

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

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University Clinical Centre of Serbia, University of Belgrade (14.09.2023/No 341/7).

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

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Mijajlović, V., Miler, M., Ilić, R. et al. Oncogene-induced senescence in meningiomas—an immunohistochemical study. J Neurooncol 166, 143–153 (2024). https://doi.org/10.1007/s11060-023-04532-y

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