TRKA expression and NTRK1 gene copy number across solid tumours

Gianluca Mauri, Emanuele Valtorta, Giulio Cerea, Alessio Amatu, Michele Schirru, Giovanna Marrapese, Vincenzo Fiorillo, Patrizia Recchimuzzo, Ivana Stella Cavenago, Erica Francesca Bonazzina, Valentina Motta, Calogero Lauricella, Silvio Veronese, Federica Tosi, Martina Maiolani, Giuseppe Rospo, Mauro Truini, Emanuela Bonoldi, Jason Christiansen, Steven J. PottsSalvatore Siena, Andrea Sartore-Bianchi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)926-931
Number of pages6
JournalJournal of Clinical Pathology
Volume71
Issue number10
DOIs
Publication statusPublished - Oct 1 2018

Keywords

  • fish

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Mauri, G., Valtorta, E., Cerea, G., Amatu, A., Schirru, M., Marrapese, G., Fiorillo, V., Recchimuzzo, P., Cavenago, I. S., Bonazzina, E. F., Motta, V., Lauricella, C., Veronese, S., Tosi, F., Maiolani, M., Rospo, G., Truini, M., Bonoldi, E., Christiansen, J., ... Sartore-Bianchi, A. (2018). TRKA expression and NTRK1 gene copy number across solid tumours. Journal of Clinical Pathology, 71(10), 926-931. https://doi.org/10.1136/jclinpath-2018-205124