Merlin Immunohistochemistry for Meningioma Diagnosis

• Merlin is the tumor suppressor protein encoded by the NF2 gene on chromosome 22q.
• In sporadic meningiomas, especially of lateral or convexity location and higher grade, NF2 deletions/mutations are frequent.
• Loss of merlin expression has been proposed as a surrogate immunohistochemical marker for NF2 inactivation.

• Antibodies: N-terminal, C-terminal, and phosphorylated merlin (Ser518).
• Tissue: Formalin-fixed, paraffin-embedded meningioma samples.
• Scoring: Semi-quantitative (intensity and extent of cytoplasmic staining).

• Study of 172 meningiomas, with 20 having known NF2 status.
• All tumors showed some level of merlin immunoreactivity, including phosphorylated merlin.
• Phospho-merlin was more expressed in meningothelial subtypes.
• No consistent correlation between IHC merlin expression and NF2 mutation/deletion.
• No clear association with WHO grade or clinical outcome

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• Widely available and low-cost.
• Morphological correlation possible.
• Phospho-merlin gives insights into functional status of merlin.

• No strong correlation with NF2 gene alterations.
• Phosphorylated merlin may be misleading (inactive form still stains).
• Variability in IHC interpretation and scoring.
• Risk of non-specific staining.

• Merlin IHC is not a reliable surrogate marker for NF2 mutation.
• Should not replace molecular techniques (NGS, FISH).
• Can be used as supportive information in context (e.g., NF2-related meningiomatosis).
• Most useful in research and subtype analysis.

Merlin immunohistochemistry offers biological insight into meningiomas but lacks the specificity and predictive value required for routine use as a surrogate for NF2 status. Molecular confirmation is essential.