EXPRESSION OF ALPHA-GALNAC GLYCOPROTEINS BY BREAST CANCERS

The expression of complex carbohydrates recognised by Helix pomatia le ctin (HPA, nominal monosaccharide binding specificity alpha-GalNAc) ha s been shown to predict unfavourable prognosis in breast and other can cers. It has been suggested that the prognostic significance of HPA bi nding may be through recognition of either Tn epitope (alpha-GalNAc-O- serine/threonine) or blood group A antigen (terminal alpha-1-->3GalNAc attached to the basic H-antigen, Fuc-alpha-1-->2-Gal-beta-1-->4(or 3) GlcNAc-->R). In this study, the expression of glycoproteins terminati ng in alpha-GalNAc residues was investigated immunohistochemically usi ng HPA and two monoclonal antibodies - BRIC 66 (anti-alpha-GalNAc) and BRIC 111 (anti-Tn). In paraffin sections, 74/87 (85%) of breast cance rs expressed HPA-binding ligands, while 28/87 (32%) were positive for BRIC 66 binding and 25/87 (29%) expressed Tn. Distribution of staining patterns were distinctive acid different with the three markers. BRIC 66, BRIC 111 and HPA binding to glycoproteins derived from breast can cer homogenates and to blood group A and Tn positive glycoproteins in Western blots confirmed the immunohistochemistry data. The results sug gest that the prognostic significance of HPA binding in breast cancer is unlikely to be simply through recognition of blood group A antigen or Tn epitope on cancer cells. Breast cancers may express a complex pr ofile of related but distinct glycans sharing similar terminal immunod ominant sugar GalNAc, which may be implicated in aggressive biological behaviour.