Increased Expression of Thomsen-Friedenreich Antigens during Tumor Progression in Breast Cancer Patients

Abstract

Paraffin-embedded tissue sections of primary tumors and lymph node metastases of 80 breast cancer patients were tested for the expression of Thomsen-Friedenreich (TF) antigens with the aid of a monoclonal IgM antibody (49H8) highly specific for phenyl-beta-galactoside. TF antigens were not expressed in 16 different normal tissues with the exception of some structures in the kidney. In tumor cells, two types of antigen expression were found; namely, cryptic and exposed. From stage T1/No to stages T2–4/N1,2 the number of cases expressing high amounts of TF antigens increased from 9% (2/22) to 22% (4/18) while the percentage of patients with low intensity of antibody binding was reduced from 59% (13/22) to 39% (7/18). The total amount of TF-positive primary tumors at stages T2–4/No increased from 42% (8/19) to 69% (18/26) when lymph nodes were infiltrated (T2–4/N1,2). At this stage 80% (21/26) of the patients with lymph node infiltration carried TF antigens in the nodes. The distribution of antigens was heterogeneous among the tumor cells and was expressed mainly in an apical or luminal position. The increased expression of antigens was attributed to exposed TF antigens, while cryptic antigens remained constant. When primary tumors expressed exposed TF antigens, the corresponding lymph nodes also contained exposed antigen. The same was true for the cryptic antigen. The data demonstrate an increase in the intensity of TF antigen expression during tumor progression and a spread of TF-positive tumor cells into the axillary lymph nodes with an increasing number of breast cancer patients being TF-positive at this stage.

Simple mucin-type carbohydrate antigens (T, sialosyl-T, Tn and sialosyl-Tn) in breast carcinogenesis

“…This discrepancy probably reflects the different sensitivities of antibodies and lectins used in most studies [12,17,25,27]. We found T antigen expression not only in morphologically normal epithelial cells adjacent to carcinomas as shown by Reed et al .…”

“…The demonstration of T (Thomsen-Friedenreich) antigen in breast epithelium is variable from series to series [12,17,25,27]. This discrepancy probably reflects the different sensitivities of antibodies and lectins used in most studies [12,17,25,27].…”

Characterisation of disseminated tumor cells in the bone marrow of breast cancer patients by the Thomsen–Friedenreich tumor antigen

“…In addition, TF expression was always accompanied with MUC1 expression suggesting that MUC1 is the carrier protein for TF also in DTC-BM. Surprisingly, 98% of all DTC-BM found by CK staining were also positive for TF, although only 40-70% of invasive primary breast cancers are positive for this antigen (Wolf et al 1988). In that study, the number of cases expressing high amounts of TF antigens increased from 9% in stage T1/N0 to 22% in stage T2-4/N1,2.…”

“…In several tumor entities, for example gastric, colon (Baldus et al 2000), lung (Takanami 1999) or cancer of the cervix uteri (Hirao et al 1993), a correlation between TF expression and negative prognosis could be demonstrated. Also in breast cancer, a correlation between high tumor stage and TF expression was observed (Wolf et al 1988) and TF expression predicted worse survival (Imai et al 2001). Results obtained in our study show that TF is also expressed on DTC-BM of breast cancer patients.…”

Prognostic impact of Thomsen–Friedenreich tumor antigen and disseminated tumor cells in the bone marrow of breast cancer patients

“…Yet, its prognostic impact in other tumors, especially in breast cancer, is indeterminate. A correlation between high tumor stage and TF expression was observed [24], whereas in another study high TF expression predicted improved survival [25].…”