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Published on: February 17, 2022
Pan-TRK Immunohistochemistry: An Example-Based Practical Approach to Efficiently Identify Patients With NTRK Fusion
Esther Conde1, Susana Hernandez2, Elena Sanchez2
1From Pathology and Laboratory of Therapeutic Targets, Hospital Universitario HM Sanchinarro, HMHospitales, CIBERONC, Madrid, Spain (Conde, Lopez-Rios).
Context.—:
Food and Drug Administration-approved TRK inhibitors with impressive overall response rates are now available for patients with multiple cancer types that harbor NTRK rearrangements, yet the identification of NTRK fusions remains a difficult challenge. These alterations are highly recurrent in extremely rare malignancies or can be detected in exceedingly small subsets of common tumor types. A 2-step approach has been proposed, involving a screening by immunohistochemistry (IHC) followed by a confirmatory method (fluorescence in situ hybridization, reverse transcriptase-polymerase chain reaction, or next-generation sequencing) in cases expressing the protein. However, there is no interpretation guide for any of the available IHC clones.
Objective.—:
To provide a pragmatic update on the use of pan-TRK IHC. Selected examples of the different IHC staining patterns across multiple histologies are shown.
Data Sources.—:
Primary literature review with PubMed, combined with personal diagnostic and research experience.
Conclusions.—:
In-depth knowledge of pan-TRK IHC will help pathologists implement a rational approach to the detection of NTRK fusions in human malignancies.
Insights
Identifying NTRK fusions is crucial for targeted cancer therapy. This update provides guidance on using pan-TRK immunohistochemistry (IHC) to improve the detection of these challenging genetic alterations in various tumors.
Area of Science:
- Oncology
- Pathology
- Molecular Diagnostics
Background:
- TRK inhibitors are effective treatments for cancers with NTRK rearrangements.
- Identifying NTRK fusions is challenging due to their rarity in specific cancer types.
- Current diagnostic approaches involve a two-step screening and confirmation process.
Purpose of the Study:
- To offer a practical update on the application of pan-TRK immunohistochemistry (IHC).
- To illustrate diverse IHC staining patterns across different cancer histologies.
Main Methods:
- Comprehensive literature review utilizing PubMed.
- Incorporation of diagnostic and research expertise in pan-TRK IHC.
Main Results:
- Pan-TRK IHC serves as a valuable screening tool for NTRK fusions.
- Specific staining patterns can aid in the interpretation of IHC results.
- Examples across multiple histologies are presented to guide pathologists.
Conclusions:
- Expertise in pan-TRK IHC is essential for pathologists.
- A rational approach to detecting NTRK fusions can be implemented.
- Improved detection facilitates the use of targeted TRK inhibitor therapies.
