@article {Maurijclinpath-2018-205124, author = {Gianluca Mauri and Emanuele Valtorta and Giulio Cerea and Alessio Amatu and Michele Schirru and Giovanna Marrapese and Vincenzo Fiorillo and Patrizia Recchimuzzo and Ivana Stella Cavenago and Erica Francesca Bonazzina and Valentina Motta and Calogero Lauricella and Silvio Veronese and Federica Tosi and Martina Maiolani and Giuseppe Rospo and Mauro Truini and Emanuela Bonoldi and Jason Christiansen and Steven J Potts and Salvatore Siena and Andrea Sartore-Bianchi}, title = {TRKA expression and NTRK1 gene copy number across solid tumours}, elocation-id = {jclinpath-2018-205124}, year = {2018}, doi = {10.1136/jclinpath-2018-205124}, publisher = {BMJ Publishing Group}, abstract = {Aims Neurotrophic Tropomyosin Kinase Receptor 1 (NTRK1) gene encodes for the protein Tropomyosin-related kinase A (TRKA). Deregulated activity of TRKA has been shown to have oncogenic potential. We present here the results of an immunohistochemical (IHC) observational cohort study of TRKA expression together with gene copy number (GCN) assessment in various solid tumours.Methods Formalin-fixed, paraffin-embedded consecutive samples of different tumour types were tested for TRKA expression. Samples showing TRKA IHC staining in at least 10\% of cells were analysed by fluorescence in situ hybridisation to assess NTRK1 gene rearrangements and/or individual GCN gain. All patients underwent this molecular assessment within the phase I ALKA-001 clinical trial.Results 1043 samples were tested and annotation for histology was available in 1023. Most of the samples were colorectal adenocarcinoma (CRC) (n=550, 52.7\%) and lung adenocarcinoma (n=312, 29.9\%). 24 samples (2.3\%) were biliary tract carcinoma (BTC). Overall, 17 (1.6\%) samples were characterised by TRKA IHC expression (four weak, eight moderate, five strong): 9/17 lung adenocarcinoma, 3/17 CRC, 3/17 BTC, 1/17 thyroid cancer and 1/17 cancer of unknown primary. Of these, 1/17 with strong TRKA IHC staining displayed NTRK1 gene rearrangement and 15/17 NTRK1 GCN gain by FISH. No correlation was found between intensity of TRKA IHC staining and number of copies of NTRK1.Conclusions TRKA expression can be found in 1.6\% of solid tumours and can be paralleled by NTRK1 gene rearrangements or mostly GCN gain. The prognostic and translational therapeutic impact of the latter remains to be established.}, issn = {0021-9746}, URL = {https://jcp.bmj.com/content/early/2018/05/25/jclinpath-2018-205124}, eprint = {https://jcp.bmj.com/content/early/2018/05/25/jclinpath-2018-205124.full.pdf}, journal = {Journal of Clinical Pathology} }