Overexpression of vitamin D receptor indicates a good prognosis for cholangiocarcinoma

Abstract

Up-regulation of vitamin D receptor (VDR) expression has been shown in several tumors and is thought to represent an important endogenous response to tumor progression. The authors aimed to verify the expression of VDR and its clinical significance in histologically proven cholangiocarcinoma (CCA). The antiproliferative activity of vitamin D3 on CCA cell lines was explored. The immunohistochemistry of 111 paraffin-embedded CCA tissues showed that VDR expression gradually increased during CCA development. Normal bile duct epithelium rarely expresses VDR, whereas more than 74% of CCA tissues showed positive VDR staining, of which 40% were high. Approximately 80%-90%of CCA patients with papillary and well differentiated adenocarcinomas had positive VDR expression in tumor tissues, whereas 39% positive VDR expression was found in those with poorly differentiated CCAs (P < .001). Expression of VDR was shown to be compatible with an overall favorable prognosis for CCA. Treatment with 1,25(OH)(2)D(3), an active metabolite of vitamin D3, in the CCA cell lines with high expression of VDR significantly reduced cell proliferation in a dose-dependent manner. The effect was not demonstrated in the CCA cell lines that had lower VDR expression. These data indicated an active role for VDR in mediating the antiproliferative effects of 1,25(OH)(2)D(3) in CCA cell lines. VDR expression may constitute an important prerequisite for using vitamin D and/or its analogs in the treatment of CCA. Investigation of a mechanism by which VDR and its ligand mediate these processes is needed to provide the basis for the potential use of this hormone and its derivatives in the prevention and treatment of CCA.