Abstract
BackgroundIn cancer patients, MUC1 glycoprotein may carry Lewis y which could be involved in immune response. Purposes: 1- to evaluate the presence of Lewis y and MUC1 in circulating immune complexes (Lewis y/CIC and MUC1/CIC, respectively) and their correlation; 2- to analyze the possible presence of Lewis y in carbohydrate chains of tumoral MUC1 glycoprotein and 3- to correlate serum and tissue parameters considered.MethodsPretreatment serum and tissue breast samples from 76 adenocarcinoma, 34 benign and 36 normal specimens were analyzed. Anti-MUC1 and anti-Lewis y MAbs were employed. To detect Lewis y/CIC and MUC1/CIC, ELISA tests were developed; serum samples containing MUC1 were previously selected by Cancer Associated Serum Antigen (CASA). Immunoprecipitation (IP) was performed in 9 malignant, benign and normal samples and analyzed by SDS-PAGE and Western blot. Lewis y and MUC1 expression was studied by immunohistochemistry (IHC). Statistical analysis was performed employing principal component analysis (PCA), ANOVA, Tukey HSD, Chi square test and classical correlation (p < 0.05).ResultsBy ELISA, Lewis y/IgM/CIC levels showed statistically significant differences between breast cancer versus benign and normal samples; mean ± SD values expressed in OD units were: 0.525 ± 0.304; 0.968 ± 0.482 and 0.928 ± 0.447, for breast cancer, benign disease and normal samples, respectively, p < 0.05. Lewis y/IgG/CIC did not show any statistically significant difference. MUC1/IgM/CIC correlated with Lewis y/IgM/CIC. By CASA, 9 samples with MUC1 values above the cut off were selected and IP was performed, followed by SDS-PAGE and Western blot; bands at 200 kDa were obtained with each MAb in all the samples. By IHC, with C14 MAb, 47.5%, 31% and 35% of malignant, benign and normal samples, respectively, showed positive reaction while all the samples were positive with anti-MUC1 MAb; in both cases, with a different pattern of expression between malignant and non malignant samples.ConclusionOur findings support that in breast cancer there was a limited humoral immune response through Lewis y/IgM/CIC levels detection which correlated with MUC1/IgM/CIC. We also found that Lewis y might be part of circulating MUC1 glycoform structure and also that Lewis y/CIC did not correlate with Lewis y expression.
Highlights
In cancer patients, Mucin 1 (MUC1) glycoprotein may carry Lewis y which could be involved in immune response
In order to continue the study of blood group related Lewis antigen involvement in breast cancer, we have focused this research on the difucosylated Lewis y antigen; this carbohydrate belongs to the ABH Lewis blood group family which is overexpressed on the majority of carcinomas including ovary, pancreas, prostate, breast, colon and non small cell lung cancers [25,26,27]
In this study by IHC, with this Monoclonal antibody (MAb), we found a positive reaction in 47.5% of breast tumor samples, showing a different pattern of expression among malignant, benign and normal samples; ; no statistically significant difference in percentage of expression was found
Summary
MUC1 glycoprotein may carry Lewis y which could be involved in immune response. In order to decrease mortality and to improve treatment, prevention and early detection biomarkers are object of study. In this sense, it is very important to increase knowledge about tumor biology, which includes studies on risk factors, tumor development, dissemination and metastasis. There is sufficient evidence that blood group related Lewis antigens are tumor-associated molecules [1]. Changes in the structure of glycan chains covalently attached to glycoproteins and glycolipids are a common feature of progression to malignancy [2]. In O-linked glycosylation, the glycans are added to serine and threonine hydroxyl groups. The epitopes recognized by antibodies related to the ABO and Lewis blood group antigens are found in this region. Some sulphation of sugars in terminal structures may occur [4]
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