The substantial loss of H3K27me3 can stratify risk in grade 2, but not in grade 3 meningioma

Abstract

Trimethylation of lysine 27 of histone H3 (H3K27me3) has recently emerged as a crucial epigenetic marker in meningioma. The loss of H3K27me3 expression might predict the early recurrence of grade 1 and 2 meningiomas. However, this is controversial in terms of grade 3 meningioma and the effects of H3K27me3 on the overall survival (OS) of patients with low low-grade meningioma have not been studied. Therefore, we immunohistochemically assessed the prognostic implications of H3K27me3 expression in grade 2 and 3 meningiomas. Whole-slide H3K27me3 immunostaining was evaluated for strict quality control and to confirm a significant correlation (P < .0001) with tissue microarray results. The effects of tissue age on H3K27me3 immunostaining were also evaluated, to select an appropriate cohort for survival analysis. Log-rank tests of 115 grade 2 meningiomas and 26 grade 3 meningiomas showed that the loss of H3K27me3 expression was a prognostic factor for early recurrence (P < .0001) and death (P = .00012) in grade 2, but not in grade 3 meningioma. Multivariate analysis revealed that age, recurrent tumor, and loss of H3K27me3 expression (hazard ratio, 1.264 -7.510; P = .0133) were significant for recurrentrecurrence-free survival (RFS), and that recurrent tumor and loss of H3K27me3 expression (hazard ratio, 1.717-120.621; P Z .0140) were significant for OS. We concluded that H3K27me3 expression is a significant prognostic factor for the RFS and OS of patients with grade 2 meningioma; it should be considered as an ancillary test for risk stratification of this meningioma.