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

BackgroundBreast 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 methodsWe 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.ResultsALDH1A3+/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) (pDFS < 0.001; pOS < 0.001). The negative clinical outcomes in ALDH1A3+/CD44+ tumors were further confirmed by a multivariate analysis using Cox proportional hazard models (pDFS < 0.001, HR = 3.155; pOS = 0.001, HR = 3.193). This was also true with respect to the clinical treatment regimens of chemotherapy (pDFS < 0.001; pOS = 0.001), radiotherapy (pDFS = 0.004; pOS = 0.004), and endocrine therapy (pDFS < 0.001; pOS < 0.001).ConclusionIn 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.