Abstract
BACKGROUND: Perineural invasion is a common path for cholangiocarcinoma (CCA) metastasis, and it is highly correlated with postoperative recurrence and poor prognosis. It is often an early event in a disease that is commonly diagnosed in advanced stages, and thus it could offer a timely therapeutic and diagnostic target if better understood. This article systematically reviews the progress of CCA neural invasion-related molecules. METHODS: Studies were identified by searching MEDLINE and PubMed databases for articles from January 1990 to December 2009, using the keywords "cholangiocarcinoma," "perineural invasion," "nerve growth factor"(NGF), "neural cell adhesion molecule" (NCAM), "matrix metalloproteinase"(MMP), "neurotransmitter," "acetylcholine" (Ach), and "transforming growth factor" (TGF)." Additional papers and book chapters were identified by a manual search of references from the key articles. RESULTS: From above we found that the molecules NGF, NCAM, MMP, Ach and TGF may have prognostic significance in, and offer clues to the mechanism of CCA neural invasion. CONCLUSIONS: Cholangiocarcinoma's increasing worldwide incidence is especially poignant in view of both the lacking effective therapies, and the fact that it is commonly diagnosed in advanced stages. As CCA neural invasion often appears early, more complete characterization of its molecular pathology could lead to the identification of targets for the diagnosis and therapy of this devastating malignancy.