Purpose: The expression of the carcinoma-associated mucin MUC-1 is thought to be restricted to epithelial cells and is used for micrometastatic tumor cell detection in patients with solid tumors, including those with breast cancer. Little is known, however, about the expression of MUC-1 epitopes in normal hematopoietic cells. Materials and Methods: MUC-1 expression was analyzed by flow cytometry and immunocytology on bone marrow (BM) mononuclear cells and purified CD34+ cells from healthy volunteers, using different anti-MUC-1–specific monoclonal antibodies. In addition, Western blotting of MUC-1 proteins was performed. Results: Surprisingly, 2% to 10% of normal human BM mononuclear cells expressed MUC-1, as defined by the anti–MUC-1 antibodies BM-2 (2E11), BM-7, 12H12, MAM-6, and HMFG-1. In contrast, two antibodies recognizing the BM-8 and the HMFG-2 epitopes of MUC-1 were not detected. MUC-1+ cells from normal BM consisted primarily of erythroblasts and normoblasts. In agreement with this, normal CD34+ cells cultured in vitro to differentiate into the erythroid lineage showed a strong MUC-1 expression on day 7 proerythroblasts. Western blotting of these cells confirmed that the reactive species is the known high molecular weight MUC-1 protein. Conclusion: Our data demonstrate that some MUC-1 epitopes are expressed on normal BM cells and particularly on cells of the erythroid lineage. Hence the application of anti–MUC-1 antibodies for disseminated tumor cell detection in BM or peripheral blood progenitor cells may provide false-positive results, and only carefully evaluated anti–MUC-1 antibodies (eg, HMFG-2) might be selected. Furthermore, MUC-1–targeted immunotherapy in cancer patients might be hampered by the suppression of erythropoiesis. J Clin Oncol 17: 1535–1544. 1999 by American Society of Clinical Oncology.

MICROMETASTATIC TUMOR cells in bone marrow (BM) aspirates represent an independent prognostic factor in a variety of malignancies, including carcinoma of the breast, gastrointestinal tract, lung, and neuroblastoma. 1–6 In the context of autologous BM or peripheral blood progenitor cell (PBPC) transplantation, the detection of contaminating tumor cells is of crucial importance7–9 since micrometastatic tumor cells may contribute to disease recurrence after high-dose chemotherapy and autologous stem cell transplantation. 10, 11 Epithelial tumor cell detection in BM or PBPC preparations is performed by immunocytochemistry or polymerase chain reaction–based technology. The primary antigens of interest include cytokeratin components, HER-2/neu, the human epithelial antigen HEA 125, or members of the carcinoembryonic antigen family. 12, 13 Another target molecule used for the detection of micrometastatic tumor cells, particularly in breast cancer, is the carcinoma-associated mucin MUC-1. 1, 14