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.
Clinical Research Design and Statistical Services, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, Australia.
Pathology. 2021 Jun;53(4):470-477. doi: 10.1016/j.pathol.2020.08.009. Epub 2020 Nov 2.
Nerve growth factor (NGF) and its receptors, the neurotrophic receptor tyrosine kinase 1 (NTRK1/TrkA) and the common neurotrophin receptor (NGFR/p75), 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.
神经生长因子（NGF）及其受体，神经营养受体酪氨酸激酶 1（NTRK1/TrkA）和共同神经营养因子受体（NGFR/p75），越来越多地被牵连到癌症的进展中，但它们在食管癌中的临床病理意义尚不清楚。在这项研究中，通过免疫组织化学分析了 303 例食管癌与 137 例正常食管组织中的 NGF、NTRK1 和 NGFR 的表达。对免疫染色进行了数字量化，并与临床病理参数进行了比较。在食管癌细胞和正常食管组织中均发现了 NGF 和 NGFR 染色，且染色水平相似。NGFR 染色随着分级略有增加（p=0.0389）。有趣的是，NTRK1 染色在食管鳞状细胞癌中明显升高（OR 2.31，95%CI 1.13-4.38，p<0.0001），在腺癌中显著降低（OR 0.50，95%CI 0.44-0.63，p<0.0001）与正常食管组织相比。此外，与 1 级相比，NTRK1 染色在 2 级和 3 级（OR 0.51，95%CI 0.21-1.40，p<0.0001）中降低，表明该受体优先参与食管鳞癌的分化形式。这些数据共同表明，NTRK1 是食管鳞状细胞癌的生物标志物和候选治疗靶点。
