The Emerging Relevance of H3K27 Trimethylation Loss in Meningioma: A Systematic Review of Recurrence and Overall Survival with Meta-Analysis.

Abstract

It has been proposed in the most recent 2021 World Health Organization classification of brain tumors that the loss of trimethylation at histone 3 lysine site 27 (H3K27me3) might prognosticate meningioma outcomes. However, to date, the emerging literature has remained diffuse in its stance. Thus, the aim of the present study was to determine the prognostic relevance of H3K27me3 loss in meningioma. Searches of 7 electronic databases from inception to October 2021 were conducted in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. Articles were screened against prespecified criteria. Outcomes were pooled by random effects meta-analyses of proportions, where possible. A total of 7 retrospective cohort studies satisfied all the criteria, with a total of 2180 meningioma patients overall (1291 male patients [59%]; mean age, 56 years). Across all 7 studies, the pooled incidence of H3K27me3 loss was estimated at 15% (95% confidence interval, 8%-24%). Across 6 studies, the pooled multivariate-derived hazard ratio estimate for recurrence was 1.77 (95% confidence interval, 1.23-2.31; P < 0.01). Overall survival on univariate analysis was significantly shorter with H3K27me3 loss in 2 of 4 studies (50%), and 2 studies had described a significant association between H3K27me3 loss and shorter overall survival on multivariate analysis. The contemporary metadata favor a greater incidence of meningioma recurrence based independently on H3K27me3 loss, with a statistically significant difference. It is possible that these effects are more pronounced for grade 2 meningiomas; however, more robust data and analysis are needed to augment this position.