Clinicopathological significance of S 100 protein expression in cholangiocarcinoma

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 S 100 proteins in the multistep cholangiocarcinogenesis to clarify their clinicopathological significance. Methods Immunohistochemical analysis was performed for the expression of S 100 A 2, S 100 A 4, S 100 A 6, and S 100 P . Bile concentrations of S 100 P were measured using enzyme‐linked immunosorbent assay. Results The immunohistochemical expression of the S 100 proteins was increased in biliary intraepithelial neoplasia as well as invasive adenocarcinoma of perihilar cholangiocarcinoma. Among the proteins, S 100 P expression was most drastically increased during the multistep carcinogenesis process. In cases with perihilar and extrahepatic cholangiocarcinoma, the immunohistochemical expression of S 100 A 2 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 S 100 P were increased significantly in patients with cholangiocarcinoma compared with those in patients with lithiasis. Receiver operating characteristic curve analysis showed that S 100 P bile concentration was an indicator of cholangiocarcinoma with a sensitivity of 93% and a specificity of 70%. Conclusions These results suggest that S 100 P may be useful for the detection of cholangiocarcinoma as tissue and bile biomarkers, and the immunohistochemical expression of S 100 A 2 is a potential prognostic marker in cholangiocarcinoma patients.