Aberrant expression of CD44 in bile duct cancer correlates with poor prognosis

CCD44, a transmembrane glycoprotein receptor, plays significant roles in cell migration, differentiation, and survival signaling which are important for both normal and cancer cells. In this study, we examined the expression of all isoforms of CD44 by immunohistochemistry in 3 cases of biliary cystadenoma, 15 cases of non-invasive cystadenocarcinoma (CAC) bile duct tumors, and 67 cases of the aggressive bile duct tumor, cholangiocarcinoma (CCA). Normal bile duct epithelia at different segments along the biliary tree did not express CD44. However, normal biliary cells of the large bile duct adjacent to tumor areas and dysplastic biliary cells in CCA tissues were positive. CD44 was not expressed in cystadenomas and the majority of CACs. Two CAC cases with short survival and the majority of CCA aberrantly expressed CD44. These observations suggest important roles for CD44 in the early stage of carcinogenesis and progression of bile duct cancer. Regardless of the type of bile duct tumor, CAC or CCA patients with positive CD44 expression in biliary epithelia had significant shorter survival than those with negative CD44. Aberrant expression of CD44 in CAC or CCA tissues may indicate an unfavorable patient outcome and may serve as a useful practical adjunct to conventional prognostic indicators for bile duct cancer.