Expression of MUC-1 epitopes on normal bone marrow: Implications for the detection of micrometastatic tumor cells

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 c ancer. 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(+) c ells from healthy volunteers, using different anti-MUC-1-specific monoclona l antibodies. In addition, Western blotting of MUC-1 proteins was performed . Results: Surprisingly, 2% to 10% of normal human BM mononuclear cells expre ssed MUC-1, as defined by the anti-MUC-1 antibodies BM-2 (2E11), BM-7, 12H1 2, 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 eryt hroid lineage showed a strong MUC-1 expression on day 7 proerythroblasts. W estern blotting of these cells confirmed that the reactive species is the k nown 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 t he application of anti-MUC-1 antibodies for disseminated tumor cell detecti on in BM or peripheral blood progenitor cells may provide false-positive re sults, and only carefully evaluated anti-MUC-1 antibodies (eg, HMFG-2) migh t be selected. Furthermore, MUC-1-targeted immunotherapy in cancer patients might be hampered by the suppression of erythropoiesis. J Clin Oncol 17:15 35-1544. (C) 1999 by American Society of Clinical Oncology.