Prognostic impact of Thomsen–Friedenreich tumor antigen and disseminated tumor cells in the bone marrow of breast cancer patients
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The Thomsen–Friedenreich antigen (TF, CD176) is a specific oncofetal carbohydrate epitope (Galβ1-3GalNAcα-O-Ser/Thr) expressed on the surface of various carcinomas. It mediates endothelium adhesion and formation of metastases. As it also causes immune response, its prognostic impact is indeterminate. The presence of disseminated tumor cells in the bone marrow of breast cancer patients (DTC-BM) indicates worse prognosis. We examined the expression of TF in primary breast cancer tissue of 265 patients with known BM status at the time of first diagnosis.
BM aspiration, cytospin preparation and immunocytochemical staining with the anti-Cytokeratin antibody A45 B/B3 was done following a standardised protocol. TF expression was examined immunohistochemically on Tissue Micro Arrays (TMA) with the anti-TF antibody A78-G/A7. Evaluation was done using the immunoreactive score (IRS).
Median IRS for TF expression was 2 (0–12). 68 of 265 patients (25.7%) showed DTC-BM with a median of 2/2 × 106 cells (1–1500). There was no correlation between TF expression and DTC-BM. After a median follow up of 60.1 months (7–119), the detection of DTC-BM showed prognostic significance for overall survival (OS, p = 0.034), whereas TF positivity (IRS > 2) indicated prolonged disease-free (p = 0.01), distant disease-free (p = 0.005), and overall survival (p = 0.005).
Patients with TF-positive tumors had a significantly better prognosis. Dissemination routes, TF-mediated metastasis formation, and the immunogeneity of TF might determine the prognostic impact of TF expression in different tumor entities. Further characterisation of primary tumors and DTC-BM could help to improve the biological understanding of metastases and develop targeted therapies.
KeywordsBreast cancer Disseminated tumor cells Bone marrow Minimal residual disease Thomsen–Friedenreich-antigen Prognosis Metastasis Immune response Therapy
alkaline phosphatase anti-alkaline phosphatase
distant disease free survival
disease free survival
disseminated tumor cells
epithelial platelet cell adhesion molecule
fluorescence in situ hybridisation
human epithelial growth factor receptor 2
phosphate buffered saline
tissue micro array
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We thank Mrs. S. Schulze for excellent technical assistance. We are grateful to Mrs. X. Huang for skilful TMAs preparation and Mr. S. Banares for manuscript editing.
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