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

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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.

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The 2021 WHO Classification of Tumors of the Central Nervous System: a summary

David N Louis, Arie Perry, Pieter Wesseling … (2021)

The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors. Building on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification. At the same time, it remains wedded to other established approaches to tumor diagnosis such as histology and immunohistochemistry. In doing so, the fifth edition establishes some different approaches to both CNS tumor nomenclature and grading and it emphasizes the importance of integrated diagnoses and layered reports. New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling. The present review summarizes the major general changes in the 2021 fifth edition classification and the specific changes in each taxonomic category. It is hoped that this summary provides an overview to facilitate more in-depth exploration of the entire fifth edition of the WHO Classification of Tumors of the Central Nervous System.

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Efficacy of Larotrectinib in TRK Fusion–Positive Cancers in Adults and Children

Alexander Drilon, Theodore Laetsch, Shivaani Kummar … (2018)

Fusions involving one of three tropomyosin receptor kinases (TRK) occur in diverse cancers in children and adults. We evaluated the efficacy and safety of larotrectinib, a highly selective TRK inhibitor, in adults and children who had tumors with these fusions.

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EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood

Michael Weller, Martin van den Bent, Matthias Preusser … (2020)

In response to major changes in diagnostic algorithms and the publication of mature results from various large clinical trials, the European Association of Neuro-Oncology (EANO) recognized the need to provide updated guidelines for the diagnosis and management of adult patients with diffuse gliomas. Through these evidence-based guidelines, a task force of EANO provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. The diagnostic component is based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System and the subsequent recommendations of the Consortium to Inform Molecular and Practical Approaches to CNS Tumour Taxonomy — Not Officially WHO (cIMPACT-NOW). With regard to therapy, we formulated recommendations based on the results from the latest practice-changing clinical trials and also provide guidance for neuropathological and neuroradiological assessment. In these guidelines, we define the role of the major treatment modalities of surgery, radiotherapy and systemic pharmacotherapy, covering current advances and cognizant that unnecessary interventions and expenses should be avoided. This document is intended to be a source of reference for professionals involved in the management of adult patients with diffuse gliomas, for patients and caregivers, and for health-care providers.

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Contributors

Fawaz Mohamed: URI : https://loop.frontiersin.org/people/1588842/overview

Maher Kurdi: URI : https://loop.frontiersin.org/people/1240919/overview

Saleh Baeesa: URI : https://loop.frontiersin.org/people/144379/overview

Sahar Hakamy: URI : https://loop.frontiersin.org/people/1492276/overview

Yazid Maghrabi: URI : https://loop.frontiersin.org/people/1232091/overview

Journal

Journal ID (nlm-ta): Pathol Oncol Res

Journal ID (iso-abbrev): Pathol Oncol Res

Journal ID (publisher-id): Pathol. Oncol. Res.

Title: Pathology and Oncology Research

Publisher: Frontiers Media S.A.

ISSN (Print): 1219-4956

ISSN (Electronic): 1532-2807

Publication date (Electronic): 28 February 2022

Publication date Collection: 2022

Volume: 28

Electronic Location Identifier: 1610233

Affiliations

[1] ¹ Department of Pathology , Faculty of Medicine , King Abdulaziz University , Rabigh, Saudi Arabia

[2] ² Neuromuscular and Brain Tumour Unit , King Abdulaziz University , Jeddah, Saudi Arabia

[3] ³ Division of Neurosurgery , Department of Surgery , Faculty of Medicine , King Abdulaziz University , Jeddah, Saudi Arabia

[4] ⁴ Department of Neuroscience , King Faisal Specialist Hospital , Jeddah, Saudi Arabia

[5] ⁵ Centre of Excellence of Genomic Research , King Abdulaziz University , Jeddah, Saudi Arabia

[6] ⁶ Department of Pediatrics , Faculty of Medicine , King Abdulaziz University , Rabigh, Saudi Arabia

[7] ⁷ College of Medicine , Taibah University , Almadinah Almunawwarah, Saudi Arabia

[8] ⁸ Department of Clinical Genetics , Faculty of Medicine , Al-Neelain University , Khartoum, Sudan

Author notes

Edited by: Andrea Ladányi, National Institute of Oncology (NIO), Hungary

*Correspondence: Maher Kurdi, Ahkurdi@ 123456kau.edu.sa ,

[ † ]

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Article

Publisher ID: 1610233

DOI: 10.3389/pore.2022.1610233

PMC ID: 8918486

PubMed ID: 35295612

SO-VID: ee778228-1eb9-424c-b9b6-c9f47a8ada14

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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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

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Most cited references 12

The 2021 WHO Classification of Tumors of the Central Nervous System: a summary

Efficacy of Larotrectinib in TRK Fusion–Positive Cancers in Adults and Children

EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood

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