Getting Your Laboratory on Track With Neurotrophic Receptor Tyrosine Kinase

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.