High Expression of Lewis Y/b Antigens is Associated with Decreased Survival in Lymph Node Negative Breast Carcinomas

Introduction: There is sufficient evidence that blood group related Lewis antigens are tumour-associated molecules. The Lewisy and Lewisb antigens are complex carbohydrates that are over-expressed by breast, lung, colon and ovarian cancers. The SC101 mAb is a unique Lewisy/b binding antibody that binds to native and extended Lewisy and Lewisb haptens, displaying no cross reactivity with H type 1, H type 2, Lewisx or normal blood group antigens.

Methods: Immunohistochemical detection of Lewisy/b was performed on 660 formalin-fixed, paraffin embedded breast tumour specimens using a streptavidin-biotin peroxidase technique. Tissue from these patients had previously been included in tissue microarrays. This cohort comprises a well characterized series of patients with primary operable breast cancer diagnosed between 1987 and 1992, obtained from the Nottingham Tenovus Primary Breast Carcinoma Series. This includes patients 70 years of age or less, with a mean follow up of 7 years.

Results: Of the breast carcinomas, 370 of 660 (56%) were negative for Lewisy/b expression, 110 (17%) cases showed a low level of expression (<25% of positive cells) and only 54 cases (8%) showed extensive expression of Lewisy/b (>75% of positive cells). We found significant positive associations between histological grade (p < 0.001), Nottingham Prognostic Index (p = 0.016), tumour type (p = 0.007) and the level of Lewis y/b expression. There was a significant correlation between the proportion of Lewisy/b positive tumour cells and survival in lymph-node negative patients (p = 0.006).

Conclusion: The unique epitope recognised by SC101 mAb on Lewisy/b hapten is over-expressed on breast tumour tissue compared with normal breast. In this large series of invasive breast cancers, higher expression of Lewisy/b was more often found in high grade and poor prognosis tumours compared to good prognosis cancers. Moreover, in lymph node negative breast carcinomas, over-expression of Lewisy/b hapten was associated with significantly decreased patient survival.