Clinicopathological significance of core 3 O-glycan synthetic enzyme, ß1,3-N-acetylglucosaminyltransferase 6 in pancreatic ductal adenocarcinoma.

ABSTRACT

Mucin-type O-glycans are involved in cancer initiation and progression, although details of their biological and clinicopathological roles remain unclear. The aim of this study was to investigate the clinicopathological significance of ß1,3-N-acetylglucosaminyltransferase 6 (ß3Gn-T6), an essential enzyme for the synthesis of core 3 O-glycan and several other O-glycans in pancreatic ductal adenocarcinoma (PDAC). We performed immunohistochemical and lectin-histochemical analyses to detect the expression of ß3Gn-T6 and several O-glycans in 156 cases of PDAC with pancreatic intraepithelial neoplasias (PanINs) and corresponding normal tissue samples. The T antigen, Tn antigen, sialyl Lewis X (sLeX) antigen, and sLeX on core 2 O-glycan were more highly expressed in PDAC cells than in normal pancreatic duct epithelial cells (NPDEs). Conversely, the expression of 6-sulfo N-acetyllactosamine on extended core 1 O-glycan was found in NPDEs and was low in PDAC cells. These glycan expression levels were not associated with patient outcomes. ß3Gn-T6 was expressed in ~20% of PDAC cases and 30-40% of PanINs but not in NPDEs. Higher expression of ß3Gn-T6 was found in PDAC cells in more differentiated adenocarcinoma cases showing significantly longer disease-free survival in both univariate and multivariate analyses. In addition, the expression of ß3Gn-T6 in PDAC cells and PanINs significantly correlated with the expression of MUC5AC in these cells, suggesting that ß3Gn-T6 expression is related to cellular differentiation status of the gastric foveolar phenotype. Thus, it is likely that ß3Gn-T6 expression in PDAC cells is a favorable prognostic factor in PDAC patients, and that the expression of ß3Gn-T6 correlates with the gastric foveolar phenotype in pancreatic carcinogenesis.