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
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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.
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.
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.
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.
KeywordsBiliary tract cancer Cholangiocarcinoma Neurotrophic tropomyosin receptor kinase Nerve growth factor
Biliary tract cancer
Nerve growth factor
Neurotrophic tropomyosin receptor kinase
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.
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.
For this study, participants provided informed consent when necessary.
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