Decreased expression of gastric gland mucin-specific glycan α1,4-linked N-acetylglucosamine on its scaffold mucin 6 is associated with malignant potential of pyloric gland adenoma of the stomach

Aims: Pyloric gland adenoma (PGA) is a unique gastric neoplasm expressing mucin 6 (MUC6), and is often associated with high-grade dysplasia and/or adenocarcinoma. MUC6 secreted from the gastric gland mucous cells, such as pyloric gland cells, carries unique O-glycans with terminal alpha 1,4-linked N-acetylglucosamine (alpha GlcNAc) residues on its molecule. As we recently demonstrated that alpha GlcNAc serves as a tumour suppressor for gastric adenocarcinoma, this study aimed to investigate the significance of alpha GlcNAc expression in PGA. Methods and results: Eighteen patients with PGA were examined with immunohistochemistry for aGlcNAc and MUC6. alpha GlcNAc and MUC6 were co-expressed in 12 of 18 PGAs. However, reduced aGlcNAc expression relative to MUC6 expression was observed in six cases. When the MIB-1 labelling index (LI) of tumour cells was examined with respect to reduced alpha GlcNAc expression, the MIB-1 LI was significantly higher in PGAs showing decreased aGlcNAc expression relative to MUC6 expression than in PGAs with unchanged alpha GlcNAc expression (P = 0.023). Conclusions: The present study indicates that co-expression of alpha GlcNAc and MUC6 in PGA suggests the presence of fully glycosylated MUC6 on tumour cells, consistent with pyloric gland differentiation. However, the decreased glycosylation of alpha GlcNAc on MUC6 is associated with high mitotic activity of tumour cells, indicative of malignant potential of PGA.