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Human Cancer Biology |
Authors' Affiliations: 1 Department of Pathology, Keck School of Medicine, University of Southern California; 2 Joyce Eisenberg-Keefer Breast Center, John Wayne Cancer Institute, Santa Monica, California; 3 Congressman Julian Dixon Cellular Image Core, Childrens Hospital Los Angeles Saban Research Institute, Los Angeles, California; and 4 Division of Cancer Immunotherapeutics and Tumor Immunology, City of Hope National Medical Center, Duarte, California
Requests for reprints: Richard J. Cote, Department of Pathology, University of Southern California, and Norris Comprehensive Cancer Center, Keck School of Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033. Phone: 323-865-0212; Fax: 323-865-0077; E-mail: cote_r{at}ccnt.hsc.usc.edu.
Purpose: The presence of disseminated tumor cells (DTC) in the bone marrow of breast cancer patients is an acknowledged independent prognostic factor. The biological metastatic potential of these cells has not yet been shown. The presence of putative breast cancer stem cells is shown both in primary tumors and distant metastases. These cells with a CD44+CD24–/low phenotype represent a minor population in primary breast cancer and are associated with self-renewal and tumorigenic potential. Recognizing the potential effect of prevalence of putative stem cells among DTC, we evaluated the bone marrow DTC.
Experimental Design: We employed the double/triple-staining immunohistochemistry protocol and modified the established bone marrow cytokeratin (CK) staining protocol by adding steps for additional antigens, CD44 and/or CD24. We evaluated 50 bone marrow specimens, previously categorized as CK+ from early breast cancer patients. CK+ cells were examined for CD44 and CD24 expression by light microscopy, fluorescence microscopy, and spectral imaging.
Results: We detected the putative stem cell–like phenotype in all CK+ specimens. The mean prevalence of putative stem/progenitor cells was 72% and median prevalence was 65% (range, 33-100%) among the overall DTC per patient, compared with primary tumors where this phenotype is reported in <10% of cells.
Conclusions: This is the first evidence of the existence of the putative stem-like phenotype within the DTC in bone marrow in early breast cancer patients. All patients had a putative stem cell phenotype among the DTC and most individual DTC showed such phenotype. Future molecular characterization of these cells is warranted.
Commentary
Clin. Cancer Res. 2006 12: 5606-5607.
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