Aberrant Glycosylation in Cholangiocarcinoma Demonstrated by Lectin-histochemistry

Abstract

Cholangiocarcinoma (CCA) is an aggressive malignant tumor which is difficult to diagnose at an early stage.Because no reliable CCA specific markers are available at present, most patients are diagnosed after late clinicalpresentation. In many tumors, aberrant glycans participate in various steps of pathogenesis and progression. Inthis study, we investigated aberrant glycosylation in CCA tissues using lectin histochemistry to allow associationsof specific glycans with clinicopathological features of the patients to be investigated. For this purpose, 14 lectinsspecific to 5 main glycan structures were used for screening. Nine lectins showed positive staining in hepatocytesand stromal cells in liver tissues whereas three lectins, sWGA, SJA and UEA-I, had negative lectin bindingto hepatocytes and normal bile duct epithelia but exhibited positive staining with CCA. sWGA was selectedfor further evaluation of (β-D-GlcNAc)n-glycoconjugate expressions in 44 CCA tissues. We found that sWGAspecificglycans were aberrantly expressed along with CCA development and the level of expression variedwith histological types. It was highly expressed in papillary and well-differentiated types but was significantlyreduced in poorly-differentiated lesions. Specific associations of sWGA-specific glycoconjugate expression withclinicopathological features or overall survival of patients were not apparent in this cohort study.

Keywords