EPR17341 and A7H6R pan-TRK Immunohistochemistry Result in Highly Different Staining Patterns in a Series of Salivary Gland Tumors

Abstract

Patients with NTRK-rearranged tumors can be now treated using anti-TRK-targeted therapies making NTRK testing important for treatment choices in patients with advanced cancers. Pan-TRK immunohistochemistry (IHC) could be a valuable premolecular screening strategy in this field. The choice of 1 IHC method or another requires to investigate for intermethod comparison. A high frequency of pan-TRK positive tumors among salivary gland tumors makes these tumors particularly appropriate for such a technical study. In this work, we studied the intermethod agreement for 2 pan-TRK IHC methods (using A7H6R and EPR17341 clones) in a file of salivary gland tumors of different subtypes. Among 71 tumors, pan-TRK IHC was diagnosed as positive (ie, H score ≥5) in 23 and 18 cases using EPR17341 and A7H6R clones, respectively, with a good intermethod agreement in terms of positive/negative result (κ, 0.70) but only a moderate agreement considering the H score values themselves (intraclass correlation coefficient of 0.5399). Beyond the intensity of staining and the percentages of stained cells, major differences were also observed between the location and type of cells stained in positive cases between the 2 clones. The single NTRK-rearranged case in our series (ie, a NTRK3-rearranged salivary secretory carcinoma) was positive with the 2 pan-TRK antibodies. Future studies including molecularly proven NTRK-rearranged tumors remain required to further study and compare the performances of different pan-TRK clones in the screening of NTRK-rearranged cancers but it is now obvious that the staining patterns of A7H6R and EPR17341 clones are not strictly identical.