The prognostic value of H3 K27me3 in meningiomas: A review on current evidence and methodological challenges

Meningiomas are the most common primary intracranial neoplasms. Although they mostly exhibit a benign course, some cases recur after surgery and show high morbidity and mortality rates. In addition to currently established prognostic factors, such as the extent of surgical resection and tumor grade assessed according to World Health Organization (WHO) criteria, the prognostic significance of the immunohistochemical loss of Histone 3 trimethylation in Lysine 27 (H3 K27me3) has emerged in meningiomas. This review examined original studies that analyzed the immunohistochemical expression of H3 K27me3 in meningiomas and its correlation with various features, including overall survival (OS), recurrence-free survival (RFS), and WHO grade. A literature search was conducted in PubMed for English-language publications up to July 8, 2024. Sixteen studies were included in this review. In summary, current evidence indicates that H3 K27me3 loss is more frequent in tumors exhibiting higher biological aggressiveness, as reflected by a significant association with a higher WHO grade, proliferative index, and prognostically unfavorable methylation classes. In addition, published studies consistently indicate a negative prognostic significance for progression-recurrence-free survival (PFS/RFS) in WHO grade 2 meningiomas and OS in WHO grade 3 tumors. However, the lack of a standardized definition for H3 K27me3 loss significantly hampers the incorporation of the H3 K27me3 immunohistochemical assay into routine practice to establish the prognosis of meningiomas.