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=28

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=<p><bold>Background:</bold> Neurotrophic tyrosine receptor kinase (<italic>NTRK</italic>) 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 <italic>NTRK-</italic>fusion in different brain tumours.</p><p><bold>Methods:</bold> 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, <italic>NTRK</italic>-rearrangements were tested using both DNA and RNA-based next-generation sequencing (NGS) assay using TruSight Onco500 platform.</p><p><bold>Results:</bold> The cohort included eight pilocytic astrocytomas, one oligodendroglioma, six IDH<sup>wildtype</sup> glioblastomas, four IDH<sup>mutant</sup> 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 <italic>NTRK</italic>-rearrangement. The other two positively expressed cases (liponeurocytoma and glioblastoma) were found to have <italic>NTRK2</italic>-fusions (<italic>SLC O 5A1-NTRK2, AGBL4-NTRK2, BEND5-NTRK2</italic>). All the 12 cases (100%) with no Pan-Trk expression have shown no <italic>NTRK</italic>-fusions. There was no statistically significant association between Pan-Trk expression and <italic>NTRK</italic>-fusion (<italic>p</italic> = 0.217). The detection of <italic>NTRK-</italic> fusions using NGS had high specificity over <italic>NTRK</italic>-fusion detection by using Pan-Trk IHC.</p><p><bold>Conclusion:</bold> Pan-Trk IHC is not a suitable tissue-efficient biomarker to screen for <italic>NTRK</italic>-fusions in CNS tumours, however RNA-based NGS sequencing should be used as an alternative method.</p>