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Canadian Multicentric Pan-TRK (CANTRK) Immunohistochemistry Harmonization Study
Martin D Hyrcza1, Sebastiao N Martins-Filho2, Alan Spatz3
1Department of Pathology and Laboratory Medicine, University of Calgary, Arnie Charbonneau Cancer Institute, Calgary, Alberta, Canada.
Summary
A Canadian study successfully harmonized pan-TRK immunohistochemistry (IHC) screening across 18 labs for TRK inhibitor therapy. The assay achieved high diagnostic sensitivity, enabling broader patient identification for targeted treatments.
Area of Science:
- Oncology
- Pathology
- Molecular Diagnostics
Background:
- Tumor-agnostic testing for NTRK1-3 gene rearrangements is crucial for identifying patients eligible for TRK inhibitor therapies.
- Standardized and high-quality immunohistochemistry (IHC) screening assays are needed for widespread clinical implementation.
Purpose of the Study:
- To establish and validate a high-quality pan-TRK IHC screening assay across multiple Canadian pathology laboratories.
- To assess the diagnostic sensitivity and specificity of the assay using a standardized protocol and reference materials.
Main Methods:
- A multicenter ring study involving 18 regional pathology laboratories in Canada.
- Utilized pan-TRK monoclonal antibody clone EPR17341 and centrally developed reference standards (TRK calibrators and iCAPCs).
- Laboratories optimized IHC protocols, stained 30 TRK-fusion positive/negative tumor samples, and reported staining patterns.
Main Results:
- Fifteen of 18 laboratories achieved 100% diagnostic sensitivity compared to next-generation sequencing.
- Diagnostic specificity ranged from 40% to 90%.
- Median limit of detection was 76,000 molecules/cell, with observed staining in cytoplasmic, nuclear, and membranous patterns.
Conclusions:
- The Canadian multicentric pan-TRK study successfully harmonized IHC screening, demonstrating a viable strategy for multicenter implementation.
- The developed assay achieves high diagnostic sensitivity, facilitating broader patient identification for TRK inhibitor therapies.
- Centrally developed reference materials and analytical sensitivity measurements using TRK calibrators were key to assay performance.
