2. Academic Validation
  3. The neurotrophic tyrosine kinase receptor 1 (TrkA) is overexpressed in oesophageal squamous cell carcinoma

The neurotrophic tyrosine kinase receptor 1 (TrkA) is overexpressed in oesophageal squamous cell carcinoma

  • Pathology. 2021 Jun;53(4):470-477. doi: 10.1016/j.pathol.2020.08.009.
Nathan Griffin 1,  Fangfang Gao 1,  Phillip Jobling 1,  Christopher Oldmeadow 2,  Vanessa Wills 3,  Marjorie M Walker 4,  Sam Faulkner 1,  Hubert Hondermarck 5
Affiliations

Affiliations

  • 1 School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia; Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, Australia.
  • 2 Clinical Research Design and Statistical Services, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, Australia.
  • 3 School of Public Health and Medicine, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia; Department of Surgery, John Hunter Hospital, Newcastle, NSW, Australia.
  • 4 Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, Australia; School of Public Health and Medicine, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia.
  • 5 School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia; Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, Australia. Electronic address: [email protected].
PMID: 33143904 DOI: 10.1016/j.pathol.2020.08.009
Abstract

Nerve growth factor (NGF) and its receptors, the neurotrophic receptor tyrosine kinase 1 (NTRK1/TrkA) and the common neurotrophin receptor (NGFR/p75NTR), are increasingly implicated in Cancer progression, but their clinicopathological significance in oesophageal Cancer is unclear. In this study, the expression of NGF, NTRK1 and NGFR were analysed by immunohistochemistry in a cohort of 303 oesophageal cancers versus 137 normal adjacent oesophageal tissues. Immunostaining was digitally quantified and compared to clinicopathological parameters. NGF and NGFR staining were found in epithelial cells and at similar levels between oesophageal cancers and normal oesophageal tissue. NGFR staining was slightly increased with grade (p=0.0389). Interestingly, NTRK1 staining was markedly higher in oesophageal squamous cell carcinoma (OR 2.31, 95%CI 1.13-4.38, p<0.0001) and significantly lower in adenocarcinoma (OR 0.50, 95%CI 0.44-0.63, p<0.0001) compared to normal oesophageal tissue. In addition, NTRK1 staining was decreased in grade 2 and grade 3 (OR 0.51, 95%CI 0.21-1.40, p<0.0001) compared to grade 1, suggesting a preferential involvement of this receptor in the more differentiated forms of oesophageal carcinomas. Together, these data point to NTRK1 as a biomarker and a candidate therapeutic target in oesophageal squamous cell carcinoma.

Keywords

NGF; NGF receptors; NGFR/p75(NTR); NTRK1/TrkA; Oesophageal cancer.

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