Abstract
The combination of CD44 and CD24, or aldehyde dehydrogenase 1 (ALDH1) alone, is a widely used cancer stem cell marker in breast cancer. However, no conclusion has yet been reached as to which marker is the best for characterizing cancer stemness. Immunohistochemical evaluation using cancer stem cell markers is clearly less common clinically than in basic experiments and how the expressions of these markers relate to patient outcomes remains controversial. To investigate whether combining these markers might improve the prediction of patient outcomes, we immunohistochemically examined clinical samples. Primary invasive breast cancer samples from 61 patients who eventually developed distant metastases after curative surgery were immunohistochemically examined. All patients were free of metastatic disease at the time of surgery and received standard adjuvant systemic treatments. CD44+/24- and ALDH1-positive rates in primary tumors differed according to intrinsic subtype. ER-positive patients with CD44+/24- tumors had significantly longer disease-free-survival than all other ER-positive patients (p = 0.0047). On the other hand, CD44+/24- tumors were associated with poor outcomes of ER-negative patients (p = 0.038). Finally, expression patterns of CD44 and ALDH1 in single tumors were strikingly different and there were virtually no individual double-stained cells. Thus, this combination does not allow evaluation of relationships with patient outcomes. Our results raise the possibility of CD44+/24- being a good prognostic marker, one which would allow treatment effects and outcomes to be predicted in patients with recurrent breast cancer.
Highlights
Cancer stem cells (CSCs) are defined by having the potentials to replicate and to form tumors [1,2,3]
Immunochemistry of CSCs extracted from a breast cancer cell line To test whether the antibodies for IHC employed are feasible for evaluating cancer stemness, we first stained CSCs obtained from in vitro experiments (S1 Fig)
All CD44+/CD24- cells reacted to the CD44 antibody but not to the CD24 antibody, while 88% and 22% of parental cells were positive for these markers, respectively
Summary
Cancer stem cells (CSCs) are defined by having the potentials to replicate and to form tumors [1,2,3]. Based on a number of basic studies, the combination of CD44 and CD24, or aldehyde dehydrogenase 1 (ALDH1) alone, is a widely used CSC marker in breast cancer [4, 5]. CD44-positive and CD24-negative (CD44+/24-) cells sorted according to these markers can form tumors after subcutaneous injection into immunodeficient mice[6]. Only CD44+/24- cells from breast cancer cell lines were able to form lung metastases in the in vivo experiments of another study [7]. Researchers generally choose one of these markers for study, such that totally different populations of cells might be examined according to CSC markers
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