Loss of H3K27me3 in meningiomas: an independent marker for CNS WHO grade 2?

Abstract

Accurate risk stratification for meningioma patients is challenging, particularly with borderline histology between WHO grade 1 and 2. Several molecular approaches have been proposed, but cost limit their availability. A promising marker to identify cases at higher risk of recurrence is loss of H3K27 trimethylation. However, there were insufficient data yet to incorporate it as a grading criterion into the latest WHO classification of CNS tumors 2021 (CNS5). Only 2 studies are available showing a significant association with progression-free survival, one across all WHO grades1 and one focusing on anaplastic cases.2 After the meningioma chapter for the novel WHO classification had been prepared for release, several novel studies have been published,2-6 supporting the prognostic impact of H3K27me3. Yet, none of these studies provided clear data on the clinical value to distinguish "true"grade 1 from "true"grade 2 cases, that is, cases that do not fulfill the current grade 2 criteria but still tend to early recurrence. We therefore leveraged the 2 largest of these published studies to investigate whether H3K27 trimethylation may robustly identify morphologically grade 1 tumors with outcome identical to the average grade 2 tumors. The combined cohort comprises 866 grade 1 and 317 grade 2 primary meningiomas. Loss of H3K27me3 was observed in 3.1% (27/866 cases) and 11.4% (36/317 cases) of grade 1 and 2 tumors, respectively. A median follow-up of 39 months revealed 219 recurrences.