Clinical Implications of CD44+/CD24− Tumor Cell Ratio in Breast Cancer

Abstract

To investigate the association of the CD44+/CD24- cancer stem cell (CSC) ratio with clinicopathologic features and its prognostic value in breast cancer. The CD44+/CD24- CSC ratio was determined in formalin-fixed, paraffin-embedded breast cancer tissues from 1350 breast cancer patients by double immunofluorescence staining. The Cox regression analysis was performed to evaluate whether the CD44+/CD24- CSC ratio is an independent prognostic factor. The Kaplan-Meier survival analysis was conducted to determine the association of the CD44+/CD24- CSC ratio with cancer-specific survival. The mean average CSC ratio in clinical specimens was 8.06% (range from 1.02% to 37.54%). The CD44+/CD24- CSC ratio, together with histological grade, molecular type, and clinical stage, was independent prognostic factors of breast cancer. The CD44+/CD24- CSC ratio was significantly correlated with estrogen receptor (ER), progesterone receptor (PR), and Ki67, but not the Her-2 and P53 status. Furthermore, the CD44+/CD24- CSC ratio was significantly associated with 5-year breast cancer-specific survival in 1242 cases (88.97% vs. 75.76% vs.52.11% for ≤ 5%, 5%-10% and >10% CSC ratio cases, respectively, p=0.001). The linear regression analysis showed that the CSC ratio was borderlinely correlated with the N stage related (R=0.397 p=0.06), and significantly correlated with distant recurrence (R=0.487, p=0.01) in 1350 specimens. After the survival analysis, the 5-year distant recurrence rates were (57/435 [13.10%] vs. 159/594 [26.77%] vs. 114/213 [53.52%] for ≤ 5%, 5%-10%, and >10% CSC ratio cases, p=0.001). The CSC ratio was an independent prognostic factor for breast cancer as well as a potential predictive marker for chemotherapy in breast cancer.