PT  - JOURNAL ARTICLE
AU  - Gianluca Mauri
AU  - Emanuele Valtorta
AU  - Giulio Cerea
AU  - Alessio Amatu
AU  - Michele Schirru
AU  - Giovanna Marrapese
AU  - Vincenzo Fiorillo
AU  - Patrizia Recchimuzzo
AU  - Ivana Stella Cavenago
AU  - Erica Francesca Bonazzina
AU  - Valentina Motta
AU  - Calogero Lauricella
AU  - Silvio Veronese
AU  - Federica Tosi
AU  - Martina Maiolani
AU  - Giuseppe Rospo
AU  - Mauro Truini
AU  - Emanuela Bonoldi
AU  - Jason Christiansen
AU  - Steven J Potts
AU  - Salvatore Siena
AU  - Andrea Sartore-Bianchi
TI  - TRKA expression and <em>NTRK1</em> gene copy number across solid tumours
AID  - 10.1136/jclinpath-2018-205124
DP  - 2018 Oct 01
TA  - Journal of Clinical Pathology
PG  - 926--931
VI  - 71
IP  - 10
4099  - http://jcp.bmj.com/content/71/10/926.short
4100  - http://jcp.bmj.com/content/71/10/926.full
SO  - J Clin Pathol2018 Oct 01; 71
AB  - 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.