Differential SIRT1 Expression in Hepatocellular Carcinomas and Cholangiocarcinoma of the Liver

: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are two major liver malignancies. Although some phenotypic overlap is known, HCC and CCA are usually different with regard to etiology, histology, and prognosis. Gene expression and deacetylase activity of the class III histone deacetylase SIRT1 are up-regulated in cancer cells due to oncogene overexpression or loss of function of tumor suppressor genes. SIRT1 may play a critical role in tumor initiation, progression, and drug resistance by blocking senescence and apoptosis, and promoting cell growth and angiogenesis, but pleiotropic effects (synchronous or metachronous anti-proliferation and anti-apoptotic mechanisms) have been suggested in some cancers. Our aim was to investigate the expression of SIRT1 in liver epithelial malignancies. Thirty carcinomas of the liver, including 16 HCC and 14 CCA cases, were investigated by immunohistochemistry using monoclonal antibodies against SIRT1 and p53. Western blot analysis (WBA) was carried out for expression of SIRT1 in three CCA cell lines, one HCC cell line, and one cell line of Papova-immortalized normal hepatocytes. An expression of SIRT1 was found in 11 of 16 (68.75%) HCC and in 5 of 14 (35.71%) CCA. Moreover, we found an expression of p53 in 8 out of 16 (50%) HCC and 13 out of 14 (92.86%) CCA. WBA showed expression of SIRT1 in all cell lines studied, although a stronger signal was seen in the HCC cell line. Immunohistochemical data did not correlate to clinical stage or other clinical or histopathological parameters. Sirtuin 1 is a phylogenetically-conserved family of deacetylases and our data seem to indicate that (1) pleiotropic effects may be present in hepatic epithelial malignancies, and (2) there is no specificity of SIRT1 for either HCC or CCA.