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

Exp Mol Pathol. 2016 Feb;100(1):145-50. doi: 10.1016/j.yexmp.2015.11.032. Epub 2015 Dec 11.

Abstract

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) (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).

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.

Keywords: ALDH(+)/CD44(+) cells; Breast cancer stem cell; Breast neoplasm; Metastasis; Poor prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aldehyde Oxidoreductases / genetics*
  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Disease-Free Survival
  • Female
  • Humans
  • Hyaluronan Receptors / genetics*
  • Middle Aged
  • Neoplastic Stem Cells / pathology
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Hyaluronan Receptors
  • Aldehyde Oxidoreductases
  • aldehyde dehydrogenase (NAD(P)+)