Merlin Immunohistochemistry for Meningioma Diagnosis [Neurosurgery Wiki]

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====== Merlin Immunohistochemistry for Meningioma Diagnosis ======

===== 🔬 Background =====
  * **[[Merlin]]** is the [[tumor suppressor protein]] encoded by the **[[NF2 gene]]** on [[chromosome 22]]q.
  * In **[[sporadic meningioma]]s**, 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.

===== 🧪 Immunohistochemistry Technique =====
  * **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).

===== 📊 Findings from Tollefsen et al. =====
  * 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**
((Tollefsen SE, Meta R, Solheim O, Mjønes P, Vestrheim I, Sjursen W, Torp SH. Merlin immunoreactivity fails to predict neurofibromatosis type 2 mutations in human meningiomas. J Neuropathol Exp Neurol. 2025 May 30:nlaf058. doi: 10.1093/jnen/nlaf058. Epub ahead of print. PMID: 40447281.)).

===== ⚖️ Strengths and Limitations =====

==== ✅ Strengths ====
  * Widely available and low-cost.
  * Morphological correlation possible.
  * Phospho-merlin gives insights into **functional status** of merlin.

==== ❌ Limitations ====
  * **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.

===== 📌 Clinical Implications =====
  * **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.

===== 🧠 Conclusion =====
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.**

===== 📚 References =====