Clinicopathological significance of nerves in esophageal cancer.

Abstract Nerves are emerging promoters of cancer progression, but the innervation of esophageal cancer and its clinicopathological significance remain unclear. In this study, nerves were investigated by immunohistochemistry in a cohort of 260 esophageal cancers, including 40 matched lymph node metastases and 137 normal adjacent esophageal tissues. Nerves were detected in 38% of esophageal cancers and were more associated with squamous cell carcinomas (p=0.04). The surrounding or invasion of nerves by cancer cells (perineural invasion) was detected in 12% of esophageal cancers and was associated with reduced survival (p=0.04). Nerves were found to express the NTRK1 (TRKA) and NGFR (p75NTR) receptors for nerve growth factor (NGF) and an association was suggested between high production of NGF by cancer cells and the presence of nerves (p=0.02). In vitro, NGF production in esophageal cancer cells was demonstrated by Western-blot and esophageal cancer cells were able to induce neurite outgrowth in the PC12 neuronal cells. The neurotrophic activity of esophageal cancer cells was inhibited by anti-NGF blocking antibodies. Together, these data suggest that innervation is a feature in esophageal cancers that may be driven by cancer cell-released NGF.