Multicenter Harmonization Study of Pan-Trk Immunohistochemistry for the Detection of NTRK3 Fusions

Julien Adam, Nolwenn Le Stang, Arnaud Uguen, Cécile Badoual, Marie Pierre Chenard, Sylvie Lantuéjoul, Aurélie Maran-Gonzalez, Yves Marie Robin, Philippe Rochaix, Jean Christophe Sabourin, Isabelle Soubeyran, Nathalie Sturm, Magali Svrcek, Anne Vincent-Salomon, Nina Radosevic-Robin, Frédérique Penault-Llorca

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Résumé

Pan-Trk immunohistochemistry has been described as a screening test for the detection of NTRK fusions in a broad spectrum of tumor types. However, pan-Trk testing in the clinical setting may be limited by many factors, including analytical parameters such as clones, platforms, and protocols used. This study aimed to harmonize pan-Trk testing using various clones and immunohistochemical (IHC) platforms and to evaluate the level of analytical variability across pathology laboratories. We developed several IHC pan-Trk assays using clones EPR17341 (Abcam) and A7H6R (Cell Signaling Technology) on Ventana/Roche, Agilent, and Leica platforms. To compare them, we sent unstained sections of a tissue microarray containing 9 cases with NTRK3 fusions to participating laboratories, to perform staining on Ventana/Roche (10 centers), Agilent (4 centers), and Leica (3 centers) platforms. A ready-to-use pan-Trk IVD assay (Ventana/Roche) was also performed in 3 centers. All slides were centrally and blindly reviewed for the percentage of stained tumor cells. Laboratory-developed tests with clone EPR17341 were able to detect pan-Trk protein expression in all cases, whereas lower rates of positivity were observed with clone A7H6R. Moderate to strong variability of the positive cases rate was observed with both antibodies in each IHC platforms type and each of the positivity cut points evaluated (≥1%, ≥10%, and ≥50% of stained tumor cells). The rate of false-negative cases was lower when pan-Trk staining was assessed with the lowest positivity threshold (≥1%). In conclusion, most evaluated pan-Trk IHC laboratory-developed tests were able to detect NTRK3-fusion proteins; however, a significant analytical variability was observed between antibodies, platforms, and centers.

langue originaleAnglais
Numéro d'article100192
journalModern Pathology
Volume36
Numéro de publication8
Les DOIs
étatPublié - 1 août 2023
Modification externeOui

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