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Original article
TRKA expression and NTRK1 gene copy number across solid tumours
  1. Gianluca Mauri1,2,
  2. Emanuele Valtorta1,3,
  3. Giulio Cerea1,
  4. Alessio Amatu1,
  5. Michele Schirru1,
  6. Giovanna Marrapese1,
  7. Vincenzo Fiorillo1,3,
  8. Patrizia Recchimuzzo1,3,
  9. Ivana Stella Cavenago1,3,
  10. Erica Francesca Bonazzina1,
  11. Valentina Motta1,3,
  12. Calogero Lauricella1,3,
  13. Silvio Veronese1,3,
  14. Federica Tosi1,2,
  15. Martina Maiolani1,2,
  16. Giuseppe Rospo4,
  17. Mauro Truini1,3,
  18. Emanuela Bonoldi1,3,
  19. Jason Christiansen5,
  20. Steven J Potts5,
  21. Salvatore Siena1,2,
  22. Andrea Sartore-Bianchi1,2
  1. 1 Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
  2. 2 Dipartimento di Ematologia e Onco-Ematologia, Università degli Studi di Milano, Milan, Italy
  3. 3 Department of Laboratory Medicine, Division of Pathology, Grande Ospedale Metropolitano Niguarda, Milan, Italy
  4. 4 Candiolo Cancer Institute–FPO, IRCCS, Turin, Italy
  5. 5 Ignyta Inc, San Diego, California, USA
  1. Correspondence to Dr Andrea Sartore-Bianchi, Niguarda Cancer Center, Università degli Studi di Milano, Milano, 20162, Italy; andrea.sartorebianchi{at}ospedaleniguarda.it

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.

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https://doi.org/10.1136/jclinpath-2018-205124

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    Footnotes

    • GM and EV contributed equally.

    • Handling editor Runjan Chetty.

    • Contributors GMau and EV: acquisition, analysis and interpretation of data for the study; writing the study; final approval of the version to be published. GC, MS, GMar, VF, PR, ISC, EFB, VM, CL, FT and MM: acquisition, analysis and interpretation of data for the study; final approval of the version to be published. AA: acquisition, analysis and interpretation of data for the study; writing the study; revising critically the study; final approval of the version to be published. SV, MT, EB, JC, SJP: acquisition, analysis and interpretation of data for the study; revising critically the study; final approval of the version to be published. GR: analysis and interpretation of data for the study; final approval of the version to be published. SS: acquisition, analysis and interpretation of data for the study; writing the study; revising critically the study; final approval of the version to be published. AS-B: conception and design of the study; acquisition, analysis and interpretation of data for the study; writing the study; revising critically the study; final approval of the version to be published.

    • Funding The molecular screening for NTRK1 was performed within the phase I ALKA-001 clinical trial funded by Ignyta, Inc. The study was partly supported by the grant ‘Terapia Molecolare dei Tumori’ by Fondazione Oncologia Niguarda; Associazione Italiana Ricerca Cancro grant AIRC 5 x mille Project ID 51000 Special Program Molecular Clinical Oncology; AIRC Investigator Grant Project ID 20685; AIRC 5 x mille project ID Project 21091; CORDIS Community Research and Development Information Service, grant MoTriColor, Horizon 2020 Project ID 635342.

    • Competing interests SS is a member of the Advisory Boards for Bayer and Ignyta; AS-B is a member of the Advisory Boards for Bayer. All other authors have no competing interest to declare.

    • Patient consent Obtained.

    • Ethics approval Ethical Committee of Grande Ospedale Metropolitano Niguarda.

    • Provenance and peer review Not commissioned; externally peer reviewed.