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

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.

• Authors: Nathan Griffin, Fangfang Gao, Phillip Jobling, Christopher Oldmeadow, Vanessa Wills, Marjorie M Walker, Sam Faulkner, Hubert Hondermarck
• Journal: Pathology (Pathology) Vol. 53 Issue 4 Pg. 470-477 (Jun 2021) ISSN: 1465-3931 [Electronic] England
• PMID: 33143904 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers
• NGF protein, human
• NGFR protein, human
• NTRK1 protein, human
• Nerve Tissue Proteins
• Receptors, Nerve Growth Factor
• Nerve Growth Factor
• Receptor, trkA

Topics

• Biomarkers (metabolism)
• Cohort Studies
• Epithelial Cells (metabolism, pathology)
• Esophagus (metabolism, pathology)
• Female
• Gene Expression Regulation, Neoplastic
• Head and Neck Neoplasms (metabolism, pathology)
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Nerve Growth Factor (genetics, metabolism)
• Nerve Tissue Proteins (genetics, metabolism)
• Receptor, trkA (genetics, metabolism)
• Receptors, Nerve Growth Factor (genetics, metabolism)
• Squamous Cell Carcinoma of Head and Neck (metabolism, pathology, therapy)
• Tissue Array Analysis