DETECTION OF CIRCULATING ANTI-MUC1 MUCIN CORE PROTEIN ANTIBODIES IN PATIENTS WITH COLORECTAL-CANCER

MUC1 mucin has a unique immunogenic peptide epitope in the extracellul ar domain, which has been shown to induce humoral and cellular immune response. In this study, we evaluated the pathophysiological significa nce of circulating anti-MUC1 mucin core protein IgG antibodies (anti-M UC1 antibodies) in colorectal cancer by Western blot analysis and Cr-5 1 release assay. Anti-MUC1 antibodies were detected in 5 of 31 (16.1%) healthy subjects and in 27 of 56 (48.2%) patients with colorectal can cer. The presence of circulating anti-MUC1 antibodies was not signific antly correlated with the level of circulating antigen MUSE11 or with other clinicopathological parameters tested. The incidence of positivi ty for anti-MUC1 antibodies in stage I and II (staged according to the General Rules Sar Clinical and Pathological Studies on Cancer of the Colon and Rectum of the Japanese Research Society for Cancer of the Co lon and Rectum) cancers was 45.5% and 58.8%. respectively, suggesting that positivity for these antibodies may be of use as an adjunct for t he diagnosis of colorectal cancer in the early stages in the absence o f serious complications such as liver diseases. Because of the epitope similarity, anti-MUC1 antibodies in the serum may function in a manne r similar to that of anti-MUC1 peptide monoclonal antibodies (mAbs). W e therefore observed antibody-dependent cell mediated cytotoxicity wit h anti-MUCl peptide mAb using MUC1 cDNA-transfected colon cancer CHC-Y 1 cells as the target. The decreased sensitivity of MUC1 transfectants to effector cells was restored to a level equivalent to that in contr ol cells. These data suggest that the detection of circulating anti-MU C1 antibodies may be a useful adjunct for the early diagnosis and immu nological analysis of colorectal cancer.