Down-regulation of nerve growth factor in poorly differentiated and advanced human esophageal cancer

Background: Binding of nerve growth factor (NGF) to its receptor TrkA leads to intracellular tyrosine kinase activation and regulates the growth and d ifferentiation of various nonneuronal tumours, Patients and Methods: In the present study NGF and TrkA were analysed by Northern blot analysis in situ hybridisation and immunohistochemistry in 41 esophageal cancer samples in comparison to normal controls. Results. NGF mRNA (P<0.01), but not TrkA mRN A was down-regulated in esophageal cancer samples compared with normal tiss ues. In the normal esophagus NGF mRNA and protein was present ill epithelia l cells of the entire epithelial layer and TrkA mRNA and protein was presen t in epithelial cells of the basal layer. In esophageal cancer NGF and TrkA mRNA and protein were present in the cancer cells. Down-regulation of NGF correlated with poor differentiation (P<0.01) and advanced tumour stage (P< 0.01). Low TrkA expression was related to advanced tumour stage (P<0.05). C onclusion: A loss of activation of the NGF/TrkA pathway occurs during tumou r progression and may contribute to loss of tumour differentiation in esoph ageal cancer.