Expression of sialyl Lewis^a relates to poor prognosis in cholangiocarcinoma

摘要

AIM: High levels of serum sialyl Lewisa (sLea) are frequently found in cholangiocarinnoma (CCA) patients and have been suggested to be a serum marker for CCA. However, the significance of this antigen in CCA is unknown. In this study,the clinical significance of sLea expression in CCA tissues and the possible role of sLea in vascular invasion in vitro were elucidated.METHODS: Expression of sLea in tumor tissues of 77patients with mass-forming CCA and 33 with periductal infiltrating CCA was determined using immunohistochemistry.The in vitro assays on adhesion and transmigration of CCA cells to human umbilical vein endothelial cells were compared between CCA cell lines with and without sLea expression.RESULTS: sLea was aberrantly expressed in 60% of CCA tumor tissues. A significant relationship was found between the frequency of sLea expression and the mass-forming type CCA (P = 0.041), well differentiated histological grading (P = 0.029), and vascular invasion (P = 0.030). Patients with positive sLea expression had a significantly poorer prognosis (21.28 wk, 95% CI = 16.75-25.81 wk) than those negative for sLea (37.30 wk, 95% CI = 27.03-47.57 wk)(P＜0.001). Multivariate analysis with adjustment for all covariates showed that patients positive for sLea possessed a 2.3-fold higher risk of death than patients negative for sLea (P＜0.001). The role of sLea in vascular invasion was demonstrated using in vitro adhesion and transmigration assays. KKU-M213, a human CCA cell-line with a high expression of sLea, adhered and transmigrated to IL-1β-activated endothelial cells of the human umbilical vein more than KKU-100, the line without sLea expression (P＜0.001).These processes were significantly diminished when the antibodies specific to either sLea or E-selectin were added to the assays (P＜0.001).CONCLUSION: This study demonstrates the clinical significance of sLea expression in vascular invasion, and an unfavorable outcome in CCA. The role of sLea in vascular invasion which may lead to poor prognosis is supported by the in vitro adhesion and transmigration studies.