Humoral immune response to abnormal MUC1 in subjects with colorectal adenoma and cancer

Colorectal cancer (CRC) expresses a hypoglycosylated (abnormal) form of MUC1 different than MUC1 expressed in normal colon, which elicits antibodies in patients with CRC. This form of MUC1 is expressed in other abnormal but non-malignant lesions in the colon, such as adenomatous polyps, precursors to CRC. Estimates of the prevalence of anti-MUC1 antibodies in subjects with these lesions are lacking. We evaluated IgM and IgG anti-MUC1 antibodies in 148 subjects with non-advanced adenomas (NAA), advanced adenomas (AA), colorectal cancer, hyperplastic polyps (HPP), and normal controls. We hypothesized that the prevalence of anti-MUC1 antibodies would increase along the adenoma-carcinoma sequence as more dysplastic tissues express more abnormal MUC1. Anti-MUC1 IgM was found in 5/47 (10.6%) of normals, 5/45 (11.1%) of NAA, 7/47 (14.9%) of AA, and 4/20 (20.0%) of CRC (p=0.70). The prevalence of anti-MUC1 IgG was 8/47 (17.0%) of normals, 14/45 (31.1%) of NAA, 14/47 (29.8%) of AA, and 6/20 (30.0%) of CRC (p=0.36). We found no significant differences in the prevalence of anti-MUC1 antibodies between subjects along the adenoma-carcinoma sequence. However, in an exploratory analysis, the median normalized anti-MUC1 IgG OD level of the combined abnormal groups (NAA, AA, CRC) was significantly higher than the normals (0.045 OD vs. 0.030 OD; p=0.017). Our data support further studies into the potential role of anti-MUC1 immunity in preventing progression of premalignant colon lesions to colon cancer.