Coexpression of MUC1 mucin peptide core and the thomsen-friedenreich antigen in colorectal neoplasms

BACKGROUND: Controversial findings have been reported regarding the expression of the Thomsen-Friedenreich (TF) antigen in colorectal neoplasms when different monoclonal antibodies (MoAbs) have been used. Moreover, there is no information available regarding the carrier protein(s) of this antigen. METHODS: Forty-five colorectal adenomas and 48 carcinomas were studied by avidin-biotin complex-peroxidase immunohistochemistry. The immunohistochemistry employed the MoAb BW835, which was reactive to a carrier specific and site specific TF antigen on MUC1 mucin, as well as reference antibodies directed to MUC1 (HMFG2) or MUC2 core peptides (4F1) and directed to TF antigen irrespective of its carrier (A78-G/A7, peanut agglutinin). To evaluate the coexpression of different epitopes by the same antigen, sandwich enzyme-linked immunoadsorbent assays were performed. RESULTS: Although MUC1 peptide antigen and MUC1-bound TF antigen were not detectable in normal or transitional mucosa surrounding colorectal neoplasms, expression of these antigens in adenomas accompanied the development of high grade dysplasia. By contrast, MUC2 expression detected by the MoAb 4F1 was inversely correlated with the progression of the adenoma-carcinoma sequence. In well- and moderately differentiated colorectal carcinomas, the neo-expressed TF antigen is predominantly bound to MUC1. This feature could be demonstrated by antigen coexpression using peptide and the TF antigen specific MoAbs. However, in mucinous carcinomas exhibiting a weak MUC1 peptide expression in most specimens, the presence of TF antigen on the MUC2 peptide core cannot be ruled out. CONCLUSIONS: TF antigen is strongly coexpressed with MUC1 mucin peptide core in the colorectal adenoma-carcinoma sequence, resulting in well- and moderately differentiated carcinomas. Only in mucinous carcinomas may it be coexpressed with MUC2 antigen.