Immunoreactivity of Thomsen-Friedenreich (TF) antigen in human neoplasms: The importance of carrier-specific glycotope expression on MUC1

On the basis of their known fine specificities we evaluated the immunohisto chemical marker qualities of two monoclonal antibodies (mabs) defining the tumor-associated TF disaccharide Gal beta 1-3GalNAc. This antigen is expres sed in certain tumors in correlation with prognosis and metastasis. The rea ctivity of one of these mabs (A78-G/A7) depends on clustered TF disaccharid es (glycosylation at vicinal Ser/Thr positions) while the other - mab BW835 - has been characterized to bind specifically to TF disaccharide linked to a motif within the MUC1 repeat. Therefore, mab BW835 represents an interes ting tool for the identification of tumor-associated glycoforms of MUC1, wh ich are involved in tumor progression and metastasis, but also in the recog nition of tumor cells by cytotoxic T cells. As references the TF-binding lectins from peanut (PNA) and Artocarpus integ rifolia (jacalin) were applied. The binding patterns of these immunoreagent s were strikingly distinct. Mab BW835 showed a significantly stronger react ivity than mab A78-G/A7, especially in gastric, mammary, pancreatic, thyreo ideal, renal and bladder carcinomas. PNA and jacalin receptors exhibited an expression in the majority of all cancer types, with the exception of semi noma and glioblastoma/sarcoma. These results can be explained by the broade r fine specificities of the lectins. Furthermore, a strong expression of MU C1-bound TF antigen is indicated by the staining pattern of mab BW835. The marker qualities of both antigens, TF and MUC1, are combined in the binding specificity of BW835, and hence this antibody may have a high impact for t he immunodetection of these tumor-associated antigens.