ALDH+/CD44+ cells in breast cancer are associated with worse prognosis and poor clinical outcome

Background: Breast cancer stem cells (BCSCs) play essential roles in tumor metastasis and contribute to remarkably negative clinical outcomes. Recently, aldehyde dehydrogenase (ALDH) and CD44 positivity (ALDH(+)/CD44(+)) was identified as a marker of BCSCs in vitro/in vivo studies. The aim of this study was to evaluate the prevalence of ALDH(+)/CD44(+) cells in breast cancer and the association of these two markers with clinicopathological features and clinical outcomes. Materials and methods: We investigated the prevalence of ALDH1A3(+)/CD44(+) cells in a cohort of 144 formalin-fixed, paraffin-embedded (FFPE) breast cancer tissues. The tissues were stained for ALDH1A3 and CD44 by single and dual immunohistochemistry (dIHC). The associations among the prevalence of ALDH1A3(+)/CD44 cells, the clinicopathological features and the clinical outcomes of the patients were also analyzed. Results: ALDH1A3(+)/CD44(+) cells were present in 39 patients (27.1%). By the Mann-Whitney U test, the Pearson Chi-square test or Fisher's exact test, it was demonstrated that the prevalence of ALDH1A3(+)/CD44(+) cells was closely correlated with larger tumor size (p = 0.001), nodal metastasis status (p = 0.043), more advanced clinical stage (p = 0.021) and distant metastasis after initial surgery (p = 0.001). In a univariate survival analysis, the presence of ALDH1A3(+)/CD44(+) tumor cells had a significant negative association with both disease-free survival (DFS) and overall survival (OS) (p(DFS) < 0.001; p(OS) < 0.001). The negative clinical outcomes in ALDH1A3(+)/CD44(+) tumors were further confirmed by a multivariate analysis using Cox proportional hazard models (p(DFS) < 0.001, HR = 3.155; p(OS) = 0.001, HR = 3.193). This was also true with respect to the clinical treatment regimens of chemotherapy (P-DFS < 0.001; p(OS) = 0.001), radiotherapy (p(DFS) = 0.004; p(OS) = 0.004), and endocrine therapy (p(DFS) < 0.001; p(OS) < 0.001). Conclusion: In summary, our results indicate that the prevalence of ALDH1A3(+)/CD44(+) tumor cells in breast cancer is significantly associated with worse prognostic factors and favors a poor prognosis. (C) 2015 Elsevier Inc. All rights reserved.