Molecular prognostication in grade 3 meningiomas and p16/MTAP immunohistochemistry for predicting status.

BACKGROUND

The World Health Organization 2021 classification introduces molecular grading criteria for anaplastic meningiomas, including promoter () mutations and homozygous deletion. Additional adverse prognostic factors include H3K27me3 and BAP1 loss. The aim of this study was to explore whether these molecular alterations stratified clinical outcomes in a single-center cohort of grade 3 meningiomas. Additionally, we examined whether p16 and MTAP immunohistochemistry can predict status.

METHODS

Clinical and histopathological information was obtained from the electronic medical records of grade 3 meningiomas resected at a tertiary center between 2007 and 2020. Molecular testing for mutations and copy-number status, methylation profiling, and immunohistochemistry for H3K27me3, BAP1, p16, and methylthioadenosine phosphorylase (MTAP) were performed. Predictors of survival were identified by Cox regression.

RESULTS

Eight of 15 cases demonstrated elevated mitotic index (≥20 mitoses per 10 consecutive high-power fields), 1 tumor exhibited BAP1 loss, 4 harbored mutations, and 3 demonstrated homozygous deletion. Meningiomas with mutations and/or homozygous deletion showed significantly reduced survival compared to anaplastic meningiomas with elevated mitotic index alone. Immunohistochemical loss of p16 and MTAP demonstrated high sensitivity (67% and 100%, respectively) and specificity (100% and 100%, respectively) for predicting status.

CONCLUSIONS

Molecular alterations of grade 3 meningiomas stratify clinical outcomes more so than histologic features alone. Immunohistochemical loss of p16 and MTAP show promise in predicting status.