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Getting Your Laboratory on Track With Neurotrophic Receptor Tyrosine Kinase
Frederick Inglis Rudolf Eyerer1, Georganne Bradshaw2, Patricia Vasalos2
1From the Department of Pathology and Laboratory Medicine, University of Vermont Medical Center; Burlington (Eyerer).
Context.—:
Neurotrophic receptor tyrosine kinase (NTRK) fusion testing has both diagnostic and therapeutic implications for patient care. With 2 tumor-agnostic US Food and Drug Administration-approved tropomyosin receptor kinase (TRK) inhibitors, testing is increasingly used for therapeutic decision making. However, the testing landscape for NTRK fusions is complex, and optimal testing depends on the clinicopathologic scenario.
Objective.—:
To compare different NTRK testing methods to help pathologists understand test features and performance characteristics and make appropriate selections for NTRK fusion detection for their laboratory and individual patient specimens.
Data Sources.—:
A literature search for NTRK gene fusions and TRK protein was performed, including papers that discussed treatment, testing methodology, and detection or prevalence of fusion-positive cases.
Conclusions.—:
As standard of care in some tumor types, next-generation sequencing (NGS) panel testing is a cost effective and reliable way to detect a broad range of NTRK fusions. The design of the panel and use of DNA or RNA will affect performance characteristics. Pan-TRK immunohistochemistry may be used as a rapid, less expensive screen in cases that will not undergo routine NGS testing, or on specimens unsuitable for NGS testing. Fluorescence in situ hybridization may be appropriate for low-tumor-content specimens that are unsuitable for NGS testing. Quantitative reverse transcription polymerase chain reaction is best suited for monitoring low-level disease of a specific, previously identified target. This information should help laboratories develop a laboratory-specific NTRK testing algorithm that best suits their practice setting and patients' needs.
Insights
Neurotrophic receptor tyrosine kinase (NTRK) fusion testing is crucial for cancer care. This review compares NTRK testing methods, including next-generation sequencing (NGS) and immunohistochemistry, to guide pathologists in selecting optimal approaches for NTRK fusion detection.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Neurotrophic receptor tyrosine kinase (NTRK) fusions have significant diagnostic and therapeutic implications.
- The availability of two FDA-approved TRK inhibitors has increased the importance of NTRK fusion testing for treatment decisions.
- The landscape of NTRK fusion testing is complex, requiring careful consideration of clinicopathologic factors.
Purpose of the Study:
- To compare various NTRK testing methodologies.
- To assist pathologists in understanding the features and performance of different tests.
- To guide the selection of appropriate NTRK fusion detection methods for laboratories and patient specimens.
Main Methods:
- A comprehensive literature search was conducted on NTRK gene fusions and TRK protein.
- The search included studies on treatment, testing methodologies, and the prevalence of fusion-positive cases.
- Analysis focused on comparing the characteristics and performance of different detection techniques.
Main Results:
- Next-generation sequencing (NGS) panel testing is a cost-effective and reliable method for broad NTRK fusion detection, with performance varying by panel design and sample type (DNA/RNA).
- Pan-TRK immunohistochemistry serves as a rapid, economical screening tool for cases not undergoing routine NGS or with unsuitable specimens.
- Fluorescence in situ hybridization (FISH) is suitable for low-tumor-content specimens unsuitable for NGS, while quantitative reverse transcription polymerase chain reaction (qRT-PCR) is best for monitoring specific, low-level disease.
Conclusions:
- Optimal NTRK fusion testing depends on the specific clinical scenario and laboratory capabilities.
- Laboratories should develop tailored NTRK testing algorithms based on practice setting and patient needs.
- Understanding the nuances of each testing method (NGS, IHC, FISH, qRT-PCR) is essential for accurate and efficient NTRK fusion detection.
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