Pan‐ TRK expression and NTRK gene aberrations in meningiomas: association with tumor grade and pr

Abstract

Tropomyosin receptor kinase (TRK) fusions are actionable oncogenic drivers, and pan‐TRK immunohistochemistry (IHC) serves as a reliable screening tool for NTRK gene aberrations. However, the expression profile and clinical significance of pan‐TRK in meningiomas remain unclear. This study aimed to characterize pan‐TRK expression, its correlation with clinicopathological features, and underlying NTRK rearrangement status in meningiomas. We retrospectively analyzed 70 primary intracranial tumor specimens, including 50 meningiomas (21 WHO grade 1, 26 grade 2, and 3 grade 3) and 20 non‐meningioma CNS tumors (9 solitary fibrous tumors, 6 hemangioblastomas, and 5 schwannomas) from the First Affiliated Hospital of China Medical University (2020–2022). Pan‐TRK IHC was performed using the Ventana EPR17341 antibody, with fluorescence in situ hybridization (FISH) validating NTRK gene aberrations in positive cases. Clinicopathological correlations were analyzed using chi‐square/Fisher's exact tests and Spearman's rank correlation. Pan‐TRK immunoreactivity was detected in 12/50 (24.0%) meningiomas, predominantly with cytoplasmic staining (75.0%). Positivity was significantly higher in high‐grade (WHO 2/3) meningiomas (7/29, 46.7% versus 3/21, 14.3% in grade 1; p  = 0.031) and tumors with Ki‐67 index ≥5% (7/15, 46.7% versus 5/35, 14.3% in Ki‐67 <5%; p  = 0.027). No pan‐TRK expression was observed in non‐meningioma tumors (0/20). FISH confirmed NTRK gene aberrations in 2/12 (16.7%) pan‐TRK‐positive cases (both WHO 3 anaplastic meningiomas), with strong/moderate IHC staining correlating with aberrations. Pan‐TRK is frequently expressed in meningiomas, particularly in high‐grade and proliferative tumors, and may have preliminary utility in differentiating meningiomas from other CNS tumors. However, NTRK gene aberrations are rare, necessitating FISH or next‐generation sequencing confirmation for pan‐TRK‐positive cases to identify candidates for TRK‐targeted therapy. Further studies are needed to clarify the biological role of non‐fusion‐mediated pan‐TRK overexpression in meningioma progression.