Basic Research
Copyright ©2005 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jan 14, 2005; 11(2): 249-254
Published online Jan 14, 2005. doi: 10.3748/wjg.v11.i2.249
Expression of sialyl Lewisa relates to poor prognosis in cholangiocarcinoma
Apa Juntavee, Banchob Sripa, Ake Pugkhem, Narong Khuntikeo, Sopit Wongkham
Apa Juntavee, Sopit Wongkham, Department of Biochemistry, Faculty of Medicine and Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand
Banchob Sripa, Department of Pathology, Faculty of Medicine and Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand
Ake Pugkhem, Narong Khuntikeo, Department of Surgery, Faculty of Medicine and Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand
Author contributions: All authors contributed equally to the work.
Supported by research grants of Faculty of Medicine (#I46007), and Graduate School (#4432201), Khon Kaen University, Thailand
Correspondence to: Dr. Sopit Wongkham, Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. sopit@kku.ac.th
Telephone: +66-43-348386 Fax: +66-43-348375
Received: June 24, 2004
Revised: June 28, 2004
Accepted: July 17, 2004
Published online: January 14, 2005
Abstract

AIM: High levels of serum sialyl Lewisa (sLea) are frequently found in cholangiocarcinoma (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 77 patients 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.

Keywords: Cholangiocarcinoma; Sialyl Lewisa; Poor prognosis