The caudal-type homeodomain transcriptional factor CDX2, a member of the caudal-related homeobox gene family, plays a crucial role in the regulation of cell proliferation and differentiation in the gut. Recent studies have reported that expression of CDX2 was an independent marker of outcome in patients with resected adenocarcinoma of ampulla of Vater, gastric cancer, and colon cancer. The clinicopathological significance of CDX2 expression has hitherto remained unclear in biliary tract carcinomas (BTCs). The aim of this study was to determine whether CDX2 expression in BTCs indicates clinical outcome. The expression of CDX2 was investigated immunohistochemically in surgically resected specimens from 164 patients with BTCs, including 74 intrahepatic cholangiocarcinomas, 49 extrahepatic cholangiocarcinomas, and 41 gallbladder carcinomas. We examined the correlation between the expression of CDX2 and the clinicopathological factors, including overall survival, tumor location, tumor stage, and degree of tumor differentiation in patients with BTCs. In total, 27 out of the 164 (16.46%) BTCs expressed CDX2. The frequency of CDX2 expression was much higher in the extrahepatic cholangiocarcinomas (22.45%) and gallbladder carcinomas (29.27%) than intrahepatic cholangiocarcinomas (5.41%), the difference being statistically significant (p=0.002). Factors influencing survival on univariate analysis were tumor stage (p<0.00001), degree of tumor differentiation (p=0.0002), and CDX2 expression (p=0.01). On multivariate analysis using the Cox proportional hazard model, CDX2 expression, and tumor stage were independent prognostic factors in patients with BTCs. Expression of CDX2 was an independent indicator of outcome in patients with BTCs in addition to tumor stage and tumor differentiation. The mechanism by which CDX2 expression influences behavior of biliary tract carcinoma needs further investigation.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]