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Am J Pathol. 2018 Jan;188(1):229-241. doi: 10.1016/j.ajpath.2017.09.008. Epub 2017 Oct 14.

Neurotrophin Receptors TrkA, p75NTR, and Sortilin Are Increased and Targetable in Thyroid Cancer.

Author information

1
School of Biomedical Sciences & Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia; Hunter Medical Research Institute, University of Newcastle, Callaghan, New South Wales, Australia.
2
Hunter Medical Research Institute, University of Newcastle, Callaghan, New South Wales, Australia; School of Medicine & Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia; Department of Endocrinology, John Hunter Hospital, Callaghan, New South Wales, Australia.
3
Hunter Medical Research Institute, University of Newcastle, Callaghan, New South Wales, Australia.
4
Hunter Medical Research Institute, University of Newcastle, Callaghan, New South Wales, Australia; School of Mathematical and Physical Sciences, Faculty of Science and Information Technology, University of Newcastle, Callaghan, New South Wales, Australia.
5
Hunter Medical Research Institute, University of Newcastle, Callaghan, New South Wales, Australia; School of Medicine & Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia.
6
Hunter Medical Research Institute, University of Newcastle, Callaghan, New South Wales, Australia; School of Medicine & Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia; Department of Anatomical Pathology, John Hunter Hospital, Callaghan, New South Wales, Australia.
7
School of Biomedical Sciences & Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia; Hunter Medical Research Institute, University of Newcastle, Callaghan, New South Wales, Australia. Electronic address: hubert.hondermarck@newcastle.edu.au.

Abstract

Neurotrophin receptors are emerging targets in oncology, but their clinicopathologic significance in thyroid cancer is unclear. In this study, the neurotrophin tyrosine receptor kinase TrkA (also called NTRK1), the common neurotrophin receptor p75NTR, and the proneurotrophin receptor sortilin were analyzed with immunohistochemistry in a cohort of thyroid cancers (n = 128) and compared with adenomas and normal thyroid tissues (n = 62). TrkA was detected in 20% of thyroid cancers, compared with none of the benign samples (P = 0.0007). TrkA expression was independent of histologic subtypes but associated with lymph node metastasis (P = 0.0148), suggesting the involvement of TrkA in tumor invasiveness. Nerves in the tumor microenvironment were positive for TrkA. p75NTR was overexpressed in anaplastic thyroid cancers compared with papillary and follicular subtypes (P < 0.0001). Sortilin was overexpressed in thyroid cancers compared with benign thyroid tissues (P < 0.0001). Neurotrophin receptor expression was confirmed in a panel of thyroid cancer cell lines at the mRNA and protein levels. Functional investigations using the anaplastic thyroid cancer cell line CAL-62 found that siRNA against TrkA, p75NTR, and sortilin decreased cell survival and cell migration through decreased SRC and ERK activation. Together, these data reveal TrkA, p75NTR, and sortilin as potential therapeutic targets in thyroid cancer.

PMID:
29037860
DOI:
10.1016/j.ajpath.2017.09.008
[Indexed for MEDLINE]

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