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• W4294301254 abstract "Abstract NTRK -rearranged tumors are rare but can be successfully treated using anti-TRK–targeted therapies making NTRK testing important for treatment choices in patients with advanced cancers. Pan-Trk immunohistochemistry (IHC) has become a valuable and affordable screening tool, but the choice of antibodies and IHC protocols to investigate biomarkers is not standardized. As NTRK fusion-positive tumors are rare, systematic technical studies are sparse. Pan-Trk IHC has been reported as a fast technique for the identification of NTRK fusion driven tumors, with a reported sensitivity of about 85–90% with differences depending on which NTRK gene is involved. Furthermore, antibody specificity seems to be dependent on tumor type. In this work, we studied the intermethod agreement for four pan-Trk IHC methods, using three different clones: EPR17341 (Abcam and Ventana), EP1058Y (Abcam), A7H6R (Cell Signaling) in 18 molecularly confirmed NTRK -rearranged tumors. We further included NTRK mutated (n = 8) and amplified (N = 15) tumors as well as NTRK wild type tumors driven by other gene fusions such as ALK, ROS1 and BCOR (n = 20) and salivary gland tumors (n = 16). Among 77 tumors, pan-Trk IHC was classified as positive using an H score ≥ 5. The overall sensitivity and specificity to separate NTRK -rearranged tumors from NTRK fusion-negative tumors was 100% and 73.8%, respectively, for clone EPR17341 using an in house and the Ventana protocol. For clone A7H6R (in house protocol) we had 93.8% sensitivity and 80.3% specificity and clone EP1058Y (in house protocol) showed 73.3% sensitivity and 32.8% specificity. EPR17341 (both protocols) and A7H6R clones showed also a good interrater agreement in terms of H-score (κ = from 0.936 to 0.956) but only a moderate agreement against the reference assay (molecular data) considering positive and negative results (κ = from 0.593 to 0.591). We identified clones and assays/protocol that can be reliably used by pathologist for the screening of NTRK rearranged tumors." @default.
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• W4294301254 date "2022-09-02" @default.
• W4294301254 modified "2023-09-26" @default.
• W4294301254 title "A systematic comparison of pan-Trk immunohistochemistry assays across multiple cancer types" @default.
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• W4294301254 doi "https://doi.org/10.21203/rs.3.rs-1986852/v1" @default.
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