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.

BRAF and NRAS genetic analyses are time-consuming and can delay treatment choices in patients with metastatic melanomas presenting with acute deterioration. We compared the rapid, real-time, fully automated molecular diagnosis platform Idylla™ with next-generation sequencing (NGS) and immunohistochemistry for detection of BRAF and NRAS mutations in 36 patients with metastatic melanomas. The Idylla™ NRAS-BRAF-EGFRS492R mutation assay (110 min per sample) detected BRAF and NRAS mutations in 15 and 17 samples, respectively. One NRAS mutation was different between NGS and Idylla™ (NRASG13C vs. NRASG12A/D). Four samples were BRAF and NRAS wild-type. The global concordance between NGS and Idylla™ assays was 97.2% (35/36 cases). Immunohistochemistry was positive only in 9/9 BRAFV600E- and 6/6 NRASQ61R-mutated samples with VE1 and SP174 antibodies, respectively. The Idylla™ platform is a valuable rapid molecular diagnosis tool to reduce the delay in BRAF and NRAS analyses-related treatment choices for patients with metastatic melanoma presenting with acute deterioration.

Anti‐TRK targeted therapies offer opportunities to treat patients with advanced NTRK1/2/3‐rearranged cancers. Beyond NTRK‐rearranged secretory breast carcinomas, little is known about NTRK rearrangements and the expression of TRK proteins in non‐secretory breast carcinomas. We search for TRK proteins expressions using pan‐TRK immunohistochemistry and NTRK1, NTRK2 and NTRK3 rearrangements using fluorescent in situ hybridization (FISH) tests in a set of tissue microarray included breast carcinomas. Only 1/339 invasive breast carcinomas, the only example of secretory subtype, was positive using pan‐TRK immunohistochemistry and harboured a NTRK‐rearrangement (NTRK1 positive FISH test). According to our results, druggable NTRK rearrangements and related‐TRK proteins expression are not encountered in non‐secretory breast carcinomas.

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