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 immunohistochemical marker qualities of two monoclonal antibodies (mabs) defining the tumor-associated TF disaccharide Gal beta 1-3 GalNAc. This antigen is expressed in certain tumors in correlation with prognosis and metastasis. The reactivity of one of these mabs (A78-G/A7) depends on clustered TF disaccharides (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 interesting tool for the identification of tumor-associated glycoforms of MUC1, which are involved in tumor progression and metastasis, but also in the recognition of tumor cells by cytotoxic T cells. As references the TF-binding lectins from peanut (PNA) and Artocarpus integrifolia (jacalin) were applied. The binding patterns of these immunoreagents were strikingly distinct. Mab BW835 showed a significantly stronger reactivity than mab A78-G/A7, especially in gastric, mammary, pancreatic, thyreoideal, renal and bladder carcinomas. PNA and jacalin receptors exhibited an expression in the majority of all cancer types, with the exception of seminoma and glioblastoma/sarcoma. These results can be explained by the broader fine specificities of the lectins. Furthermore, a strong expression of MUC1-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 the immunodetection of these tumor-associated antigens.
Baldus
S E
SE
Institute of Pathology, University of Cologne, Germany. s-e.baldus@uni-koeln.de
Hanisch
F G
FG
Monaca
E
E
Karsten
U R
UR
Zirbes
T K
TK
Thiele
J
J
Dienes
H P
HP
D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D018396:Mucin-1 / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology*; D014312:Trisaccharides / Q000276:immunology*
D018985:Epitopes, B-Lymphocyte; D006023:Glycoproteins; C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D010446:Peptide Fragments; C064068:Thomsen-Friedenreich antigen, cryptic; D014312:Trisaccharides