Validation of an immunohistochemistry-based molecular group stratification of intracranial meningiomas

We sought to validate previously proposed immunohistochemistry (IHC) markers that classify meningiomas into 4 molecular groups (MG) with superior predictive ability of progression compared to World Health Organization (WHO) grade. IHC for target proteins S100B, SCGN, ACADL, and MCM2 corresponding to molecular groups 1-4, respectively, was performed on 85 surgically resected primary meningiomas across WHO grades 1-3. Additional IHC for FOXM1 was included as a potential predictor of aggressiveness. All slides were digitally analyzed for percent of cells staining positive. The primary outcome measure was time to progression. In addition, 9% cell positivity was identified as the optimal cutoff although 31% of tumors could not be classified and only 53% (n = 45) were positive for a single, unique molecular group. Within these uniquely categorized tumors, there was no significant difference in time to progression between MG1-2 versus MG3-4 (P = .7). In a separate analysis, high staining of MCM2 (MG4) was associated with shorter time to progression (P = .02). Although the previously proposed IHC targets to identify molecular groups were not meaningfully reproducible in our analysis, MCM2 staining alone correlated with shorter time to progression across all grades and may be a simple, cost-effective IHC marker to identify clinically aggressive meningiomas.