Merlin immunoreactivity fails to predict neurofibromatosis type 2 mutations in human meningiomas

Abstract

Deletion in 22q and mutations in the neurofibromatosis type 2 (NF2) gene are frequent in sporadic meningiomas. The tumor suppressor protein merlin is encoded by NF2, and mutations may promote tumor development. NF2 status is increasingly important in meningioma diagnostics and we questioned whether merlin immunohistochemistry could be used as an accessible and affordable surrogate marker for prediction of NF2 mutations. Previous studies on merlin immunoreactivity have reported diverging results. We aimed to describe the immunohistochemical expression of merlin in a large series of meningiomas and relate these findings to clinicopathological features and NF2 status. Standardized immunohistochemistry was conducted on 172 meningiomas using three different merlin antibodies directed toward the N-terminal, C-terminal and phospho-merlin (ser 518). Twenty of the included cases had known NF2 status. All tumor specimens were immunoreactive for the three merlin antibodies. The immunoreactivity of phosphorylated merlin was higher in meningothelial tumors. There were no other significant associations between merlin immunoreactivity and NF2 status, WHO grade, tumor subtype, tumor location or gender. These results indicate that merlin immunoreactivity does not seem to be predictive of NF2 mutation, as merlin was abundantly expressed by all included tumors and independently of NF2 status.

Keywords: NF2 mutation; brain tumor; diagnosis; immunohistochemistry; meningioma; merlin.

Figure 1.

Immunohistochemical imaging of merlin immunoreactivity from the same tumor specimen, with fibrosis as internal negative control: (A) antibody directed against the N-terminal (LS-C164143); (B) antibody directed against the C-terminal (ab84550); (C) antibody directed against phosphorylated merlin ser 518 (ab2478).