Decreased expression of TFF2 and decreased αGlcNAc glycosylation are malignant biomarkers of pyloric gland adenoma of the duodenum

Pyloric gland adenoma (PGA) is a duodenal neoplasm expressing MUC6 and is often associated with high-grade dysplasia and adenocarcinoma. MUC6 secreted from the pyloric gland cells carries unique O-glycans exhibiting terminal alpha 1,4-linked N-acetylglucosamine residues (alpha GlcNAc). The small peptide trefoil factor 2 (TFF2) is also secreted from pyloric gland cells and binds to alpha GlcNAc. We recently demonstrated that alpha GlcNAc serves as a tumor suppressor for gastric neoplasm including PGA, but the significance of TFF2 expression remains unknown. We examined 20 lesions representing low- and high-grade PGA in 22 cases by immunohistochemistry for alpha GlcNAc, TFF2, MUC6, MUC5AC, MUC2 and p53. alpha GlcNAc, TFF2 and MUC6 were co-expressed on the cell surface and a dot-like pattern in the cytosol in low-grade PGA lesions. High-grade PGA also expressed MUC6, but reduced alpha GlcNAc and TFF2 expression. The ratios of alpha GlcNAc or TFF2 to MUC6 score in high-grade PGA were significantly lower than low-grade PGA (P < 0.001). Co-expression of alpha GlcNAc-glycosylated MUC6 and TFF2 in PGA suggests the existence of alpha GlcNAc/TFF2 form complex in PGA cells, a finding consistent with our observations in non-neoplastic Brunner's gland cells. The decreased alpha GlcNAc and TFF2 expression are associated with high grade atypical cells, indicative of the malignant potential of PGA.