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Background:  Neurotrophic tyrosine receptor kinase ( NTRK ) fusion has been detected in rare types of CNS tumours, which can promote tumorigenesis. The efficacy of Trk inhibitor became a significant therapeutic interest. Our aim was to investigate whether Pan-Trk immunohistochemistry (IHC) is a reliable and efficient marker for detecting  NTRK- fusion in different brain tumours.   Methods:  This study included 23 patients diagnosed with different types of CNS tumours. Testing for Pan-Trk IHC with monoclonal Ab (EPR17341) has been performed on all FFPE tissues. Parallelly,  NTRK -rearrangements were tested using both DNA and RNA-based next-generation sequencing (NGS) assay using TruSight Onco500 platform.   Results:  The cohort included eight pilocytic astrocytomas, one oligodendroglioma, six IDH wildtype  glioblastomas, four IDH mutant  grade four astrocytomas, and one sample of each (astroblastoma, central neurocytoma, medulloblastoma, and liponeurocytoma). The mean age was 35 years; seven cases were in the paediatric age group, and 16 were adult. Pan-Trk expression was detected in 11 (47.8%) tumours, and 12 (52.1%) tumours showed no Pan-Trk expression. Nine Cases (82%) with different Pan-Trk expressions did not reveal  NTRK -rearrangement. The other two positively expressed cases (liponeurocytoma and glioblastoma) were found to have  NTRK2 -fusions ( SLC O 5A1-NTRK2, AGBL4-NTRK2, BEND5-NTRK2 ). All the 12 cases (100%) with no Pan-Trk expression have shown no  NTRK -fusions. There was no statistically significant association between Pan-Trk expression and  NTRK -fusion ( p  = 0.217). The detection of  NTRK-  fusions using NGS had high specificity over  NTRK -fusion detection by using Pan-Trk IHC.   Conclusion:  Pan-Trk IHC is not a suitable tissue-efficient biomarker to screen for  NTRK -fusions in CNS tumours, however RNA-based NGS sequencing should be used as an alternative method.

pathology and oncology research/pathology oncology research

The Diagnostic Value of Pan-Trk Expression to Detect Neurotrophic Tyrosine Receptor Kinase (NTRK) Gene Fusion in CNS Tumours: A Study Using Next-Generation Sequencing Platform