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Neurotrophic tropomyosin receptor kinase (NTRK) and nerve growth factor (NGF) are not expressed in Caucasian patients with biliary tract cancers: pooled data from three independent cohorts

  • C. B. WestphalenEmail author
  • A. Preinfalk
  • S. Kruger
  • M. Haas
  • B. W. Renz
  • M.-O. Riener
  • A. Weber
  • T. Kirchner
  • J. Werner
  • V. Heinemann
  • M. von Bergwelt-Baildon
  • H. A. Baba
  • J. T. Siveke
  • S. Ormanns
  • S. Boeck
Brief Research Article
  • 27 Downloads

Abstract

Background

Neuronal signaling has been implicated in the pathophysiology of multiple malignancies. In biliary tract cancers (BTCs), tumor cell expression of nerve growth factor (NGF) and its receptor neurotrophic tropomyosin receptor kinase (NTRK) has been reported in Asian patients and linked to inferior clinical outcome. Furthermore, NTRK fusions have emerged as a promising target in various cancers. Expression patterns of these markers in Caucasian patients remain unknown.

Methods

In this study, 106 patients with BTCs were included. Immunohistochemistry for pan-NTRK and NGF-beta was performed on > 90 samples of this cohort. Additionally, samples from two independent cohorts, incorporating 254 cases, were used to confirm the findings of the original cohort.

Results

While expression of pan-NTRK and NGF-beta was readily detectable in peri-tumoral nerves, these markers were not detectable in malignant epithelial cells in our cohort.

Conclusions

In a large cohort of Caucasian patients with BTC, NTRK and NGF-beta were not detectable, underscoring potential differences between Caucasian and Asian patient populations.

Keywords

Biliary tract cancer Cholangiocarcinoma Neurotrophic tropomyosin receptor kinase Nerve growth factor 

Abbreviations

BTC

Biliary tract cancer

ECC

Extrahepatic cholangiocarcinoma

FFPE

Formalin-fixed, paraffin-embedded

ICC

Intrahepatic cholangiocarcinoma

NGF

Nerve growth factor

NTRK

Neurotrophic tropomyosin receptor kinase

TMA

Tissue microarray

Notes

Authors’ contribution

CBW: Design of the study, data analysis, writing of the manuscript; provided funding; AP: study design, data collection, data analysis; SK: data collection, intellectual input, critical discussion of the manuscript, MH: data collection, manuscript writing; BWR: data collection, discussion of the manuscript, technical support; MOR: provided materials (TMA) and patient data, writing and discussion of the manuscript; AW: provided patient materials (TMA) and patient data; TK: provided patient materials for TMA construction, critical discussion of the manuscript; JW: provided patient data; VH: study design, manuscript writing; MvB: provided patient data, writing and discussion of the manuscript; HAB: provided patient materials (TMA) and patient data; discussion and writing of the manuscript; JTS: provided patient materials (TMA) and patient data; discussion and writing of the manuscript; SO: construction of TMA; TMA staining, data analysis; SB: study design, project management, writing and discussion of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethics approval

This retrospective study was carried out according to the recommendations of local authorities, the local ethics committee of the Medical Faculty of the University of Munich (Approval Number 285-15) and of the Medical Faculty of the University Duisburg-Essen (Approval Number 13-5638-BO) and in accordance with the Declaration of Helsinki.

Informed consent

For this study, participants provided informed consent when necessary.

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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  • C. B. Westphalen
    • 1
    • 2
    Email author
  • A. Preinfalk
    • 1
  • S. Kruger
    • 1
  • M. Haas
    • 1
  • B. W. Renz
    • 3
  • M.-O. Riener
    • 4
    • 5
  • A. Weber
    • 6
  • T. Kirchner
    • 7
  • J. Werner
    • 3
  • V. Heinemann
    • 1
    • 2
  • M. von Bergwelt-Baildon
    • 1
    • 2
  • H. A. Baba
    • 8
  • J. T. Siveke
    • 9
    • 10
  • S. Ormanns
    • 7
  • S. Boeck
    • 1
    • 2
  1. 1.Department of Medicine III, University HospitalLudwig Maximilian UniversityMunichGermany
  2. 2.Comprehensive Cancer Center MunichMunichGermany
  3. 3.Department of Surgery, University HospitalLudwig Maximilian UniversityMunichGermany
  4. 4.OptiPath, Pathology Joint PracticeFrankfurtGermany
  5. 5.Institute of PathologyUniversity Hospital Erlangen-NurembergErlangenGermany
  6. 6.Department of Pathology and Molecular PathologyUniversity Hospital ZürichZurichSwitzerland
  7. 7.Institute of Pathology, Faculty of MedicineLudwig Maximilian UniversityMunichGermany
  8. 8.Institute of PathologyUniversity Hospital EssenEssenGermany
  9. 9.Division of Solid Tumor Translational Oncology (DKTK, Partner Site Essen), West German Cancer CenterUniversity Hospital EssenEssenGermany
  10. 10.German Cancer Consortium (DKTK)German Cancer Research Center (DKFZ)HeidelbergGermany

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