LEWIS C IN BREAST CANCER PROGRESSION

Abstract

Lewis C in breast cancer progressionN.A.Gadetskaya1, N.N.Tupitsyn2, N.V.Bovin3, Udalova Ya.A.11At the moment of receiving these data - FSBU “Blokhin national cancer research center” of the Russian Ministry of Health, Moscow, Russia2FSBU “Blokhin national cancer research center” of the Russian Ministry of Health, Moscow, Russia3Yu.A.Ovchinnicov and M.M.Shemiakin Institute of Bio-organic chemistry of Russian Academy of Sciences, Moscow, RussiaExact evidences on the role of natural IgM antibodies in anti-tumor immune surveillance were proved by German team of scientists (Vollmers H.P. et al.) Binding of those antibodies to tumor cells leads in many cases to malignant cell death via lipoapoptosis. In 1994, P.D. Rye & R.A. Walker produced monoclonal IgM antibody LU-BCRU-G7 against breast cancer-associated glycoprotein. In early breast cancer, expression of this marker was seen in a group of patients with poor prognosis. Antibody recognized disaccharide Galβ1- 3GlcNAc or LewisC (LeC), blood group H1-antigen precursor. We have studied glycan expression on tumor cells and antiglycan antibodies in more than 240 breast cancer patients. Immunohistochemical study in 89 cases of early breast cancer (pT1- 2 N0 M0) revealed antigen expression in 57% of cases. Expression of LeC was significantly more frequent in tumors of larger sizes (> 3 cm): 85,0% vs 48,5% (p=0,004). Expression of LeC was much more frequent in breast cancers in which lung metastases were noticed in patient's follow up (more than 1 year) after operation (p=0,047). In LeC positive cases shorter (p < 0,1) DFS (disease-free survival) was noted, differences in DFS being near significant (p = 0,05) in malignancy grade 3 and in moderate or prominent lymphoid infiltration (p=0,02), as well as long (> 4 years) patient's follow up. That data confirmed the note of Rye and Walker on poor prognosis of early LeC-positive breast cancer. In 67% of breast cancer patients small proportion of peripheral blood B-lymphocytes (up to 0,9% of B-cells) specifically bound LeC, i.e. expressed B-cell receptor for LeC. Up to 50% of these B-cells expressed CD5, so belonged to B1-natural immunity branch. Serum levels of antibodies to LeC were significantly higher in healthy woman then in breast cancer patients. Opposite relations between anti- LeC and serum levels of CA 15.3 were noticed. Membrane expression of LeC on breast cancer cells was confirmed by flow cytometry. In 36% cases patient's tumor cells were LeC -positive with low concentrations or absence of anti- LeC in sera. The last group of patients seem to be perspective in study of anti- LeC adoptive therapy approach. In conclusion. Lewis C blood group antigen expression takes place in 57% of early breast cancer, associated with poorer prognosis. Levels of anti- LeC in breast cancer patients are lower than in healthy woman, in 36% of LeC-positive cases being almost no detectable. Taking in mind important role of natural IgM antiglycan's in cancer surveillance, it seems perspective to study in this well characterized group of breast cancer patients some anti-LeC adoptive therapy to see if compensation of anti- LeC immune deficiency can be beneficial for patients.