The role of meningioma epigenetics in routine clinical practice

Abstract Background: The methylation profile of meningiomas is a promising predictive tool, potentially offering greater accuracy in assessing tumor behavior compared to WHO grading. This study aimed to evaluate the clinical relevance of routine epigenetic testing in meningioma management. Methods: We retrospectively analyzed patients undergoing meningioma resection between January 2021 and December 2023. Histopathological grading (WHO) and methylation profiling (MC) with the 850k Illumina chip were performed by an independent neuropathologist. Results: A total of 106 patients were included, with 81 (76%) classified as HO grade 1, 20 (19%) as grade 2, and 5 (5%) as grade 3. Epigenetically, 55 tumors (52%) were classified as benign, 18 (17%) as intermediate, 2 (2%) as malignant and 31 (29%) as unclassified. Discordances between WHO grading and methylation profiling were observed in 18 of 74 cases. Notably, 8 WHO grade 1 tumors (16%) displayed MC-intermediate, while 9 WHO grade 2 tumors were classified as intermediate, and 1 as malignant. Tumor board decisions were made in a median of 8 days postoperatively, guided by WHO grading; however, the epigenetic report was only available after a median of 22 days. During follow-up, 15 patients experienced tumor progression. Progression was significantly associated with the meningioma classifier (r = 0.3, p = 0.0102) and tumor volume (r = 0.4, p = 0.0005), but not with WHO grading (r = 0.17, p = 0.084). PFS in MC-unclassified tumors mirrored that of the intermediate group. Conclusion: Methylation profiling demonstrates superior predictive accuracy for meningioma progression and complements WHO grading, especially in identifying malignant maningiomas.