Prognostic significance of ACADL and MCM2 in meningiomas: Current evidence and clinical implications

This review summarizes the current evidence on the expression and prognostic significance of acyl-CoA dehydrogenase long-chain (ACADL) and minichromosome maintenance 2 (MCM2) in meningiomas. Meningiomas, which comprise approximately 41% of intracranial tumors, are classified by the World Health Organization into 15 histological subtypes and three grades of malignancy. However, owing to the biological heterogeneity within tumors of the same grade, alternative classifications based on molecular features have been proposed. One of these classifies meningiomas into four prognostically relevant molecular groups: immunogenic, benign NF2-wildtype, hypermetabolic, and proliferative. The latter two groups have the worst clinical outcomes and are enriched in ACADL and MCM2 expression, suggesting their potential as immunohistochemical surrogates. The revision of the current literature on the expression of these markers in meningiomas indicates their likely unsuitability as surrogates for molecular groups. However, MCM2 expression was consistently associated with aggressive histopathological features and reduced recurrence-free survival, emerging as a promising independent prognostic marker. ACADL also showed negative prognostic relevance, but with limited data, predominantly in grade 2 meningiomas. Both markers correlated with higher WHO grades but lacked standardized assessment criteria, limiting their clinical application. While ACADL and MCM2 immunoexpression does not reliably substitute molecular classification, MCM2, in particular, holds potential for routine prognostic use pending further validation and standardization of immunohistochemical protocols.