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Oncogene-induced senescence in meningiomas-an immunohistochemical study

J Neurooncol. 2023 Dec 20. doi: 10.1007/s11060-023-04532-y. Online ahead of print.


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.

PMID:38117375 | DOI:10.1007/s11060-023-04532-y

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