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Imaging, Diagnosis, Prognosis |
1 Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology and 2 Robert-Bosch-Hospital, Stuttgart, Germany; and 3 DEFINIENS AG, Munich, Germany
Requests for reprints: Hiltrud Brauch, Division of Molecular Mechanisms of Origin and Treatment of Breast Cancer, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, D-70376 Stuttgart; Germany. Phone: 49-711-8101-3705; Fax: 49-711-859295; E-mail: hiltrud.brauch{at}ikp-stuttgart.de.
Purpose: Breast cancer is composed of phenotypically diverse populations of cancer cells. The ability to form breast tumors has been shown by in vitro/in vivo studies to be restricted to epithelial tumor cells with CD44+/CD24/low characteristics. Validation of these findings with respect to detection in clinical samples, prognosis, and clinical relevance is in demand.
Experimental Design: We investigated breast cancer tissues for the prevalence of CD44+/CD24/low tumor cells and their prognostic value. The study included paraffin-embedded tissues of 136 patients with and without recurrences. In addition, a breast cancer progression array with normal, carcinoma in situ, and carcinoma tissues was analyzed. We applied double-staining immunohistochemistry for the detection of CD44+/CD24/low cells. Evaluation was by microscopic pathologic inspection and automated image analysis.
Results: CD44+/CD24/low cells ranged from 0% to 40% in normal breast and from 0% to 80% in breast tumor tissues. The prevalence of CD44+/CD24/low tumor cells in 122 tumors was
10% in the majority (78%) of cases and >10% in the remainder. There was no significant correlation between CD44+/CD24/low tumor cell prevalence and tumor progression. Although recurrences of tumors with high percentages of CD44+/CD24/low tumor cells were mainly distant, preferably osseous metastasis, there was no correlation with the event-free and overall survival. There was no influence on the response to different treatment modalities.
Conclusions: Our findings suggest that the prevalence of CD44+/CD24/low tumor cells in breast cancer may not be associated with clinical outcome and survival but may favor distant metastasis.
Key Words: tumor stem cells progression invasion double-staining immunohistochemistry
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