Expression of thomsen-friedenreich-related antigens in primary and metastatic colorectal carcinomas. A reevaluation

Abstract

Background. Expression of the pancarcinoma Thomsen‐Friedenreich (TF) carbohydrate antigen or, more correctly, hapten, in colorectal carcinomas is not generally agreed on. Furthermore, its suggested role in liver metastasis so far has not been substantiated by direct immunohistochemical evidence. Methods. Cryostat sections from 52 primary tumors (20 with adjacent transitional mucosa), 22 liver metastases of colorectal carcinomas, and 17 samples of normal mucosae were examined immunohistologically with a panel of at least two monoclonal antibodies (mAbs) each to TF, to its precursor, Tn, and to sialosyl‐Tn, among them two newly developed anti‐TF mAbs. Results. Of the primary colorectal carcinomas, 60% expressed TF. Staining was more intense with TF‐alpha/beta‐reactive than with exclusively TF‐alpha‐ or TF‐beta‐reactive mAbs. Normal and transitional mucosae were negative. Liver metastases were positive for TF in a significantly higher percentage of cases (91%) than primary carcinomas. Patients with TF‐positive primary tumors had a significantly higher risk to develop liver metastases compared with patients with TF‐negative tumors (57% vs. 14%, respectively). Tn and sialosyl‐Tn were expressed concomitantly in most primary (85%) and metastatic (95%) colorectal carcinomas. These antigens also were detected in transitional mucosae (Tn in 25%, sialosyl‐Tn in 55% of cases). Normal mucosae were negative. Conclusions. These results prove unequivocally the presence of exposed TF epitopes in a majority of colorectal carcinomas in which both anomers of TF are expressed. These data further suggest that TF favors liver metastasis and that its expression in primary colorectal carcinomas is a significant risk factor for the development of liver metastasis. Cancer 1995; 76:1700–8.

The Golgi Protein RCAS1 Controls Cell Surface Expression of Tumor-associated O-Linked Glycan Antigens

“…In general, TF and Tn antigens are thought to be linked with cell adhesion, invasion, and metastasis of cancer cells (34). Such glycan epitopes are normally cryptic in healthy and benign tissues, except in early embryonic stages (3).…”

C2GnT-M is downregulated in colorectal cancer and its re-expression causes growth inhibition of colon cancer cells

“…Several tumor-associated antigens have been identified on mucins (Springer, 1984;Cao et al, 1995;Fukuda, 1996;Baldus et al, 2000;Schneider et al, 2001;Hakomori, 2002). Mucin-type glycoproteins are heavily glycosylated and are mainly decorated with complex O-glycans.…”

“…T antigen (core 1 structure) and its related carbohydrate antigens, such as Tn, T, and their sialylated variants, are oncofetal carbohydrate antigens (Springer, 1984;Cao et al, 1995;Fukuda, 1996;Brockhausen, 1998Brockhausen, , 1999Baldus et al, 2000;Schneider et al, 2001;Hakomori, 2002). Changes in the expression of T antigen-related carbohydrates on cell surfaces have been observed in a variety of cancers (Hanisch and Baldus, 1997).…”

“…Changes in the expression of T antigen-related carbohydrates on cell surfaces have been observed in a variety of cancers (Hanisch and Baldus, 1997). These carbohydrate structures have been correlated with cancer metastasis and prognosis (Cao et al, 1995;Baldus et al, 2000). In addition, the interaction between T antigen and galactin-3 has been found to mediate cancer cell adhesion to endothelia (Khaldoyanidi et al, 2003).…”

Low expression of polypeptide GalNAc N-acetylgalactosaminyl transferase-3 in lung adenocarcinoma: impact on poor prognosis and early recurrence

“…In the past few years, O-linked carbohydrate antigens, such as mucin antigen (MUC1), carcinoembryonic antigen (CEA), sialyl LewisX (SLX), CA19-9, Sialyl Tn (STn), and Tn have been reported to be associated with altered adhesion (Fogel et al, 1983;Rice and Bevilacqua, 1989), invasion (Bolscher et al, 1988;Matsushita et al, 1991;Nakamori et al, 1994), recurrence, and prognosis (Itzkowitz et al, 1990;Niklinski et al, 1992;Ogawa et al, 1994;Cao et al, 1995;Diez et al, 1996;Ohgami et al, 1999) in lung cancer and other tumours. Mucin-type O-linked carbohydrates may constitute up to 80% of the total mass of these glycoproteins ; O-glycosylation has been shown to be important in the binding of cell adhesion molecules, cell differentiation, invasion, and metastasis in tumours (Nakamori et al, 1994;Clausen and Bennett, 1996;Sutherlin et al, 1997;Nomoto et al, 1999).…”