Prognostic significance and clinical impact of the Thomsen-Friedenreich antigen in gastrointestinal cancer

U Karsten, PhDa,e, Y Cao, MDb, SE Baldus, MDc, H Shigeoka, MDd, G Butschak, PhDa, A Kramer a, S Goletz, PhDa,e

aMax Delbrueck Center for Molecular Medicine, Berlin-Buch, Germany, bGerman Cancer Research Center, Heidelberg, Germany, cDepartment of Pathology, University of Cologne, Cologne, Germany, dKinki University School of Medicine, Osaka, Japan, eNemod GmbH, Berlin-Buch, Germany

Despite its long history, the Thomsen-Friedenreich (TF) oncofetal carbohydrate antigen has so far not received widespread attention among clinicians. Research in this field has for several decades been the personal domain of Georg Springer (1924-1998). In 1986 our group started with attempts to generate monoclonal antibodies towards TF, but we were not successful until 1993. In a series of sequential studies, we established that TF is expressed on 60 % of colorectal carcinomas, but not on normal colonic epithelium (including transitional epithelium) and on benign tumors, and that the expression of TF is an independent prognostic marker in patients with colorectal carcinoma. The latter finding was recently extended to gastric carcinoma. Very significantly, we found a correlation between the expression of TF on colorectal carcinomas and the risk of developing liver metastasis. Several lines of evidence suggest that asialoglycoprotein receptors are involved in the adhesion process in the liver. In an animal model, TF-mediated liver metastasis could be prevented by an anti-TF antibody. Furthermore, we examined the exact specificities, amounts and isotypes of natural anti-TF antibodies occurring in the sera of healthy individuals. We hypothesize that these antibodies may play a role in immunosurveillance. This effect could be assisted by application of anti-TF antibodies in certain critical stages, e.g. during and after surgery for colon cancer.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Prognostic Markers.