Multicenter harmonization study of pan-Trk immunohistochemistry for the detection of NTRK3 fusions.
Fiche publication
Date publication
avril 2023
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHENARD Marie-Pierre
Tous les auteurs :
Adam J, Le Stang N, Uguen A, Badoual C, Chenard MP, Lantuéjoul S, Maran-Gonzalez A, Robin YM, Rochaix P, Sabourin JC, Soubeyran I, Sturm N, Svrcek M, Vincent-Salomon A, Radosevic-Robin N, Penault-Llorca F
Lien Pubmed
Résumé
Pan-Trk immunohistochemistry (IHC) has been described as a screening test for 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 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 (LDTs) 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 LDTs were able to detect NTRK3-fusion proteins, however a significant analytical variability was observed between antibodies, platforms and centers.
Référence
Mod Pathol. 2023 04 19;:100192