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 < or =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.