Aberrant glycosylation in cholangiocarcinoma demonstrated by lectin-histochemistry

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 clinical presentation. In many tumors, aberrant glycans participate in various steps of pathogenesis and progression. In this study, we investigated aberrant glycosylation in CCA tissues using lectin histochemistry to allow associations of specific glycans with clinicopathological features of the patients to be investigated. For this purpose, 14 lectins specific to 5 main glycan structures were used for screening. Nine lectins showed positive staining in hepatocyte sand stromal cells in liver tissues whereas three lectins, sWGA, SJA and UEA-I, had negative lectin binding to hepatocytes and normal bile duct epithelia but exhibited positive staining with CCA. sWGA was selected for further evaluation of (β-D-GlcNAc)n-glycoconjugate expressions in 44 CCA tissues. We found that sWGA- specific glycans were aberrantly expressed along with CCA development and the level of expression varied with histological types. It was highly expressed in papillary and well-differentiated types but was significantly reduced in poorly-differentiated lesions. Specific associations of sWGA-specific glycoconjugate expression with clinicopathological features or overall survival of patients were not apparent in this cohort study.