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

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

doi:10.3389/pore.2022.1610233

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

Pathol Oncol Res. 2022 Feb 28:28:1610233. doi: 10.3389/pore.2022.1610233. eCollection 2022.

Authors

Fawaz Mohamed^{1

2}, Maher Kurdi^{1

2}, Saleh Baeesa³, Abdulrahman Jafar Sabbagh³, Sahar Hakamy², Yazid Maghrabi⁴, Mohammed Alshedokhi⁵, Ashraf Dallol⁵, Taher F Halawa⁶, Ahmed A Najjar⁷, Imad Fdl-Elmula⁸

Affiliations

¹ Department of Pathology, Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia.
² Neuromuscular and Brain Tumour Unit, King Abdulaziz University, Jeddah, Saudi Arabia.
³ Division of Neurosurgery, Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
⁴ Department of Neuroscience, King Faisal Specialist Hospital, Jeddah, Saudi Arabia.
⁵ Centre of Excellence of Genomic Research, King Abdulaziz University, Jeddah, Saudi Arabia.
⁶ Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia.
⁷ College of Medicine, Taibah University, Almadinah Almunawwarah, Saudi Arabia.
⁸ Department of Clinical Genetics, Faculty of Medicine, Al-Neelain University, Khartoum, Sudan.

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 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.

Keywords: CNS tumours; NTRK-fusions; Pan-Trk; TruSight Oncology500; immunohistochemistry; next-generation sequencing.

MeSH terms

Adult
Central Nervous System Neoplasms* / diagnosis
Central Nervous System Neoplasms* / genetics
Child
Gene Fusion
High-Throughput Nucleotide Sequencing
Humans
Oncogene Proteins, Fusion / genetics
Receptor, trkA* / genetics

Substances

Oncogene Proteins, Fusion
Receptor, trkA