AUTHOR=Mohamed Fawaz , Kurdi Maher , Baeesa Saleh , Sabbagh Abdulrahman Jafar , Hakamy Sahar , Maghrabi Yazid , Alshedokhi Mohammed , Dallol Ashraf , Halawa Taher F. , Najjar Ahmed A. , Fdl-Elmula Imad 

TITLE=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

JOURNAL=Pathology and Oncology Research

VOLUME=Volume 28 - 2022

YEAR=2022

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2022.1610233

DOI=10.3389/pore.2022.1610233

ISSN=1532-2807

ABSTRACT=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 tumors. 
Methods: This study included 23 patients diagnosed with different types of CNS tumours. Testing for Pan-Trk IHC with monoclonal Ab (EPR17341) was 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 8 pilocytic astrocytomas, 1 oligodendroglioma, 6 IDHwildtype glioblastomas, 4 IDHmutant grade 4 astrocytomas, and one sample of each (astroblastoma, central neurocytoma, medulloblastoma, and liponeurocytoma). The mean age was 35 years; 7 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 (SLCO5A1-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 cannot be solely used as a tissue-efficient screening biomarker to detect NTRK-fusions in CNS tumours. NTRK-fusions in CNS tumours should be tested using molecular methods.