Abstract
The expression of complex carbohydrates recognised by Helix pomatia lectin (HPA, nominal monosaccharide binding specificity alpha-GalNAc) has been shown to predict unfavourable prognosis in breast and other cancers. It has been suggested that the prognostic significance of HPA binding 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 terminating in alpha-GalNAc residues was investigated immunohistochemically using HPA and two monoclonal antibodies--BRIC 66 (anti-alpha-GalNAc) and BRIC 111 (anti-Tn). In paraffin sections, 74/87 (85%) of breast cancers 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 and different with the three markers. BRIC 66, BRIC 111 and HPA binding to glycoproteins derived from breast cancer homogenates and to blood group A and Tn positive glycoproteins in Western blots confirmed the immunohistochemistry data. The results suggest 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 profile of related but distinct glycans sharing similar terminal immunodominant sugar GalNAc, which may be implicated in aggressive biological behaviour.
Highlights
Altered glycosylation is a common feature in malignancy
It has been suggested that the prognostic significance of Helix pomatia (HPA) binding may be through recognition of either Tn epitope or blood group A antigen (terminal alpha-l-*3GaINAc attached to the basic H-antigen, Fuc-alpha-l+2-Gal-beta-I-*4(or 3) GIcNAc-*R)
The results suggest that the prognostic significance of HPA binding in breast cancer is unlikely to be through recognition of blood group A antigen or Tn epitope -on cancer cells
Summary
We have demonstrated that binding of a lectin from the Roman snail, Helix pomatia (HPA), to an unidentified carbohydrate ligand in paraffin sections of primary breast cancers is strongly associated with metastases to axillary lymph nodes and distant sites and with consequent poor patient prognosis (Leathem and Brooks, 1987; Brooks and Leathem, 1991). This observation has been confirmed by several independent studies on breast cancer (Fenlon et al, 1987; Fukutomi et al, 1989; Alam et al, 1990), and recent reports describe similar findings in gastric cancer (Kakeji et al, 1991), colorectal cancer (Schumacher et al, 1994) and prostate cancer (Shiraishi et al, 1992).
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