Immunohistochemistry as a screening tool for NTRK gene fusions: results of a first Belgian ring trial
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ORIGINAL ARTICLE
Immunohistochemistry as a screening tool for NTRK gene fusions: results of a first Belgian ring trial Koen De Winne 1 & Laure Sorber 2 & Suzan Lambin 1 & Vasiliki Siozopoulou 1,2 & Gabriela Beniuga 3 & Franceska Dedeurwaerdere 4 & Nicky D’Haene 5 & Lionel Habran 6 & Louis Libbrecht 7 & Jacques Van Huysse 8 & Birgit Weynand 9 & Katrin Wouters 10 & Patrick Pauwels 1,2,11 & Karen Zwaenepoel 1,2 Received: 11 May 2020 / Revised: 3 July 2020 / Accepted: 1 September 2020 # The Author(s) 2020
Abstract A Belgian ring trial for pan-TRK immunohistochemistry (IHC) staining was organised to harmonise pan-TRK IHC staining protocols and interpretation. As a reference method, the VENTANA pan-TRK Assay (clone EPR17341) on the Benchmark Ultra platform was selected. Six samples were selected: 2 negative, 2 fusion positive and 2 samples with wild-type endogenous TRK expression. Each participating laboratory stained the slides using their routine pan-TRK IHC and reported their results. In addition, they were asked to return one TRK-stained slide from each case. The coordinating lab evaluated these slides, compared them with the reference method and scored them. Two clones were used during the ring trial: A7H6R (Cell Signaling) and EPR17341 (Abcam/Ventana). Seven protocols achieved a sufficient performance mark, and three labs were advised to further optimise the protocol. Interpretation of pan-TRK IHC proved to be challenging in cases with physiological TRK expression. In addition, depending on the NTRK fusion partner, the staining can vary strongly in both intensity and staining pattern. Labs using the Ventana ready-to-use system based on the EPR17341 clone and using the recommended protocol settings scored best. However, given some small optimisation, all labs scored well on the technical staining and the succeeding evaluation. Keywords Immunohistochemistry . NTRK fusions . Ring trial . Cancer screening . TRK inhibitor
Introduction The neurotrophic tyrosine receptor kinases (NTRK, or commonly used TRK) are a family of transmembrane tyrosine kinases. TRKA, TRKB and TRKC proteins are encoded by the proto-oncogenes NTRK1, NTRK2, and NTRK3 respectively and are physiologically expressed in the testes, smooth
muscle and central and peripheral nervous system [1, 2]. Oncogenic fusions involving the kinase domain of the NTRK genes have been identified with high prevalence in certain rare cancers like infantile fibrosarcoma or secretory carcinoma of the breast [3]. The most common form of NTRK fusion gene, ETV6-NTRK3, is present in about 70% of infantile fibrosarcoma, making it a defining diagnostic
This article is part of the Topical Collection on Quality in Pathology * Koen De Winne [email protected] 1
Laboratory of Pathological Anatomy, Antwerp University Hospital (UZA), 2650 Edegem, Belgium
2
Center for Oncological Research Antwerp (CORE), University of Antwerp (UAntwerp), 2610 Wilrijk, Belgium
3
Institute of Pathology and Genetics, 6280 Loverval, Belgium
4
Department of Pathology, AZ Delta, 8800 Roeselare, B
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