lmmunoreactivity of Thomsen-Friedenreich ,TF, antigen in human neoplasms. The importance of carrier-specific glycotope expression on MUC

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 GalBl-3GalNAc. 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 - rnab BW835 - has been characterized to bind specifically to TF disaccharide linked to a motif within the MUCl repeat. Therefore, rnab 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 Arrocarpus integrifolia (jacalin) were applied. The binding patterns of these immunoreagents were strikingly distinct. Mab BW835 showed a significantly stronger reactivity than rnab 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 rnab 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

Lewis y antigen (CD174) and apoptosis in gastric and colorectal carcinomas, Correlations with clinical and prognostic parameters

Lewisy (Ley), also designated CD174, represents a carbohydrate blood group antigen which is strongly expressed in neoplastic gastrointestinal tissues. Previous reports indicated an association between Ley expression and apoptosis. Therefore, we tried to elucidate its clinicopathological relevance in a series of 160 gastric and 215 colorectal carcinomas by immunohistochemical detection of Ley and visualization of apoptotic cells applying the in-situ-end labelling (ISEL) method, followed by semiquantitative scoring of the specimens. In both gastric as well as colorectal carcinomas, between 40 and 50% of the cases were Ley reactive. Signet-ring cell carcinomas of the stomach exhibited a significantly stronger Ley expression compared to other tumor types. In colorectal cancers, Ley was associated with increased tumor staging, showing the strongest positivity in stage IV. Further correlations with clinicopathological variables or prognosis were not observed. On the other hand, the amount of apoptotic cells was significantly reduced in mucinous adenocarcinomas of the colorectum compared to non-mucinous carcinomas. Scoring of apoptotic cells did not result in any other clinicopathologically relevant correlations. In addition, a significant association between Ley antigen expression and apoptosis score could not be established. Therefore, the hypothesis of a functional relationship between these two aspects of gastrointestinal tumor biology is not confirmed by our data

Thomsen-Friedenreich antigen presents as a prognostic factor in colorectal carcinoma: A clinicopathologic study of 264 patients

BACKGROUND. Up to now, the expression of the tumor-associated Thomsen- Friedenreich (TF) antigen in colorectal carcinoma has not been thoroughly investigated with particular emphasis on its correlation with established clinicopathologic characteristics and classifications as well as its prognostic relevance. METHODS. Formalin fixed, paraffin embedded specimens from 264 patients with colorectal carcinoma were stained using an avidin- biotin complex-peroxidase assay. As primary monoclonal antibodies (MAbs), A78-G/A7, which binds to TFα and TFβ antigen irrespective of its carrier, and BW835, which detects TFα on MUC1 repeat peptide, were applied. RESULTS. MAbs A78-G/A7 and BW835 labeled 64.8% and 58.0%, respectively, of carcinomas. None of the binding patterns correlated with gender, tumor localization, or growth type. Only BW835 reactivity exhibited a significant correlation with increasing pTNM staging and histologic grading. Staining of the MAb A78-G/A7 was significantly stronger in carcinomas that contained a mucinous component. In univariate survival analysis, in addition to pTNM staging and histologic grading, reactivity with A78-G/A7 as well as BW835 were significantly correlated with lower survival probability. Multivariate analysis according to the Cox proportional hazards model revealed only pTNM staging, histologic grading, and A78-G/A7 staining to be independent prognostic factors. CONCLUSIONS. According to these results, TF disaccharide represents a cancer- associated antigen in colorectal carcinoma that exhibits qualities of a prognostic marker. As demonstrated by BW835 staining, it is obviously coexpressed with MUC1 peptide core in a great number of cases. These results suggest that TF, in addition to MUC1, might also serve as a useful target antigen in the treatment of patients with colorectal carcinoma