MARKERS OF PROGNOSIS IN BREAST-CANCER - THE RELATIONSHIP BETWEEN BINDING OF THE LECTIN HPA AND HISTOLOGICAL GRADE, SPF, AND PLOIDY

Abnormal cellular glycosylation as demonstrated by the binding of a le ctin from Helix pomatia (HPA) to paraffin-embedded sections has been s hown in several studies to be associated with aggressive biological be haviour and poor long-term patient prognosis in breast cancer. This st udy aims to address the possibility that expression of the HPA binding ligand may be of prognostic significance through an association with increased cellular proliferation (as measured by S-phase fraction and histological grade), anaplasia (reflected in histological grade), or p loidy (DNA index). In a 24 year retrospective study, paraffin-embedded sections of 366 primary breast cancers were stained for binding of HP A. All tumours were assessed for histological grade. Flow cytometry wa s performed on all cases for which sufficient tumour tissue was availa ble (358/366 cases) and S-phase fraction (SPF) and ploidy calculated. Data regarding patient age at diagnosis, nodal status, and tumour size were also recorded. Life table analyses revealed survival advantage f or HPA 'non stainers' in comparison to 'stainers' (p < 0.001); for pat ients with tumours of low grade vs. high grade (p < 0.001); and for th ose with tumours of low SPF vs. high SPF (p< 0.001). No survival advan tage was shown for those with diploid vs. aneuploid tumours (p = 0.17) . No association was apparent between HPA binding and grade, SPF, or p loidy (Chi squared values not significant). This was confirmed by mult ivariate analysis in which nodal status, tumour size, and SPF were ind ependently predictive of survival. There was no confounding effect of grade, SPF, or ploidy upon the correlation between survival and HPA bi nding. HPA was, however, not independently predictive owing to its str ong association with nodal status. The results of this study suggest t hat the prognostic significance of altered glycosylation, as detected by HPA binding, is unlikely to be through an association with prolifer ative rate, degree of anaplasia, or cellular ploidy, but may rather be through a direct association with the presence of nodal metastases.