• biliary intraepithelial neoplasia;
  • cholangiocarcinoma;
  • S100 protein


Background and Aim

Cholangiocarcinoma arising in the large bile ducts undergoes a multistep carcinogenesis process in chronic biliary diseases, and biliary intraepithelial neoplasia is known as a precursor lesion. This study examined the expression of S100 proteins in the multistep cholangiocarcinogenesis to clarify their clinicopathological significance.


Immunohistochemical analysis was performed for the expression of S100A2, S100A4, S100A6, and S100P. Bile concentrations of S100P were measured using enzyme-linked immunosorbent assay.


The immunohistochemical expression of the S100 proteins was increased in biliary intraepithelial neoplasia as well as invasive adenocarcinoma of perihilar cholangiocarcinoma. Among the proteins, S100P expression was most drastically increased during the multistep carcinogenesis process. In cases with perihilar and extrahepatic cholangiocarcinoma, the immunohistochemical expression of S100A2 in cholangiocarcinoma cells significantly correlated with the histological grade, lymph node metastasis, clinical stage, and a poor survival rate of the patients. The bile levels of S100P were increased significantly in patients with cholangiocarcinoma compared with those in patients with lithiasis. Receiver operating characteristic curve analysis showed that S100P bile concentration was an indicator of cholangiocarcinoma with a sensitivity of 93% and a specificity of 70%.


These results suggest that S100P may be useful for the detection of cholangiocarcinoma as tissue and bile biomarkers, and the immunohistochemical expression of S100A2 is a potential prognostic marker in cholangiocarcinoma patients.