Tissue and Serum MUC1 Mucin Detection in Breast Cancer Patients

Abstract

Tumor MUC1 expression as well as levels of MUC1, MUC1 circulating immune complexes (MUC1-CIC) and free antibodies against MUC1 (IgG and IgM-MUC1) were evaluated in 70 breast cancer patients with different stages of disease. Controls included: 135 serum samples from healthy women, normal mammary tissue samples (n = 7) and benign breast disease specimens (n = 6). In all assays, pre- and post-vaccination serum samples from breast cancer patients belonging to a vaccination protocol developed at the Memorial Sloan Kettering Cancer Center (New York, USA) were included as controls. Serum MUC1 was measured through Cancer Associated Serum Antigen test and CA15-3 test. Employing ELISA, MUC1-CIC-IgG/M were measured with either C595 or SM3 monoclonal antibodies (MAb) as catchers and also free antibodies against MUC1 (IgG and IgM) using 100mer peptide as catcher. Employing multivariate statistical analysis, results were correlated with age, tumor type, stage of disease and grade of differentiation. By quantitative immunohistochemistry using three anti-MUC1 core protein MAbs (C595, HMFG2 and SM3), tumor MUC1 was detected in 60/70 (86%) breast cancer specimens which reacted with at least one of these MAbs. High MUCI serum levels were detected in 14/67 (21%); IgG and IgM anti-MUC1 antibodies were found elevated in 32 and 14%, respectively, while IgG-MUC1-CIC-measured with C595 in 42% and IgM-MUC1-CIC in 54%; finally, SM3 was positive in 43 and 18%, respectively. Results of these studies demonstrate that in a group of breast cancer patients, MUC1 was detected both in tissue specimens as well as free in serum samples; furthermore, MUC1 can also circulate complexed with IgG and IgM antibodies; thus an accurate measurement should include free and complexed forms. On the other hand, immunohistochemical studies on breast cancer tissues may contribute to reveal different MUC1 glycoforms.

Detection of Circulating Anti-Mucin 1 (MUC1) Antibodies in Breast Tumor Patients by Indirect Enzyme-Linked Immunosorbent Assay Using a Recombinant MUC1 Protein Containing Six Tandem Repeats and Expressed in Escherichia coli

“…As for circulating anti-MUC1 IgM, stage II, III, and IV patients had slightly increased levels compared to stage I patients, an observation also noted in an earlier study (4). Therefore, there are many similarities in the changes of circulating anti-MUC1 antibodies at different stages of breast cancer before and after primary treatment, which implies these changes are related to the stages of the disease but not to the primary treatment.…”

“…A negative correlation between circulating anti-MUC1 antibodies and MUC1 antigen has been found in patients with some malignant tumors (4,20,23). In the present study, we found a significantly negative correlation between the CA15-3 (MUC1 antigen) serum level and that of the anti-MUC1 IgG antibody in patients with an advanced stage of breast cancer.…”

“…In addition, previous studies have shown that the antibodies might contribute to limit tumor outgrowth and dissemination by antibody-dependent cellular cytotoxicity (1,8,28). It is believed that free anti-MUC1 antibodies can bind MUC1 and form MUC1 circulating immune complexes (MUC1-CIC) in blood circulation (3); however, patients with stage IV of breast cancer present low MUC1-CIC, although more common anti-MUC1 antibodies and MUC1 exist in their sera (4,26). A contradictory result indicated that anti-MUC1 antibodies in stage IV of breast cancer could not bind or neutralize MUC1 antigen, and they were of low affinity (4).…”

A Review on Aptamer-Conjugated Quantum Dot Nanosystems for Cancer Imaging and Theranostic

“…Shin et al [78] reported QD based probe (emission maxima at 565 nm) covalently conjugated to MUC-1 aptamer. BOBO-3 that demonstrates significant fluorescence enhancement when intercalated into folded regions of aptamer with double helix structure was used to stain the duplex regions, resulting in the assembly of QD-aptamer conjugates over-loaded with BOBO-3 molecules.…”

Autoantibodies against the signal peptide domain of MUC1 in patients with multiple myeloma: Implications for disease diagnosis and prognosis

“…Studies investigating the role of tumor-associated antigens (TAAs) in cancer diagnosis and progression have focused on the MUC1 antigen, which is overexpressed in most solid epithelial and non-solid hematological tumors including multiple myeloma (1)(2)(3). Soluble MUC1 (sMUC1) levels were reported to be elevated in sera of patients with solid tumors such as breast carcinoma, and non-solid tumors such as multiple myeloma, using FDA approved sMUC1 assays CA15.3 and CA27.29 directed to the extracellular tandem repeat array (TRA) domain (3,4).…”