Merlin immunohistochemistry is a reliable surrogate marker for NF2 gene alterations in meningioma

Abstract

Aims: Molecular characterization as well as histologic grading has proven useful in predicting the biological behaviour of meningiomas. NF2 gene alterations, that is 22q loss and/or NF2 mutation, are the most common genetic driver events in meningioma and are associated with tumour location, histological subtype and aggressiveness. This study aimed to evaluate the utility of immunostaining for Merlin, the NF2-encoded protein, as a surrogate marker for detecting NF2 gene alterations. Methods and results: We analysed 109 CNS WHO Grade I meningiomas, comparing the Merlin immunostaining patterns with NF2 gene status. Complete loss of Merlin expression was observed in 46 of 51 (90%) meningiomas with NF2 alterations, whereas it was observed in 5 of 58 (9%) meningiomas without NF2 alterations. Therefore, Merlin immunohistochemistry could achieve relatively high sensitivity (90%, 95% confidence interval [CI]: 79%–97%) and specificity (91%, 95% CI: 81%–97%) in detecting NF2 alterations. Although some cases required careful interpretation, interobserver agreement was high at 93%. Conclusions: These findings suggest that Merlin immunohistochemistry could serve as a reliable and practical surrogate marker for NF2 alterations in meningioma. It may support molecular-based classification and risk stratification in clinical and research settings. However, caution is warranted in cases with cautery tissue damage and prominent macrophages, which can obscure staining patterns.