Decreased Gastric Gland Mucin-specific O-glycans Are Involved in the Progression of Ovarian Primary Mucinous Tumours

Abstract

Ovarian primary mucinous tumours (OPMTs) show an adenoma–borderline–carcinoma sequence with gastrointestinal metaplasia. Gastric gland mucin-specific O-glycans are unique with an α1,4-linked N-acetylglucosamine (αGlcNAc) residue attached to mucin 6 (MUC6). Although αGlcNAc is expected to be expressed in OPMTs, the relationship between αGlcNAc expression and OPMT progression remains unknown. Here, we analysed 104 areas of benign mucinous tumours (benign), 55 areas of borderline mucinous tumours (borderline), and 18 areas of malignant mucinous tumours (malignant) to investigate the expression patterns of αGlcNAc, mucin 2 (MUC2), mucin 5AC (MUC5AC), and MUC6 during the progression of OPMT from benign to malignant. MUC5AC expression was observed in all areas. The frequencies of MUC6- and αGlcNAc-positive areas were decreased with tumour progression. In particular, the decrease in αGlcNAc-positive areas was remarkable. Furthermore, αGlcNAc expression was lower than MUC6 expression at all grades (benign, p < 0.0001; borderline, p = 0.0014; malignant, p = 0.0039). Conversely, there was no difference in the expression frequency or level of MUC2 among the three grades. These results suggest that decreased expression of αGlcNAc relative to MUC6 occurs early in tumour development and marks the initiation of OPMT progression.