J Breast Cancer.  2014 Jun;17(2):121-128.

Clinicopathologic Characteristics of Breast Cancer Stem Cells Identified on the Basis of Aldehyde Dehydrogenase 1 Expression

• Kim YS
• Jung MJ
• Ryu DW
• Lee CH

Abstract

PURPOSE
Breast cancer displays varying molecular and clinical features. The ability to form breast tumors has been shown by several studies with aldehyde dehydrogenase 1 (ALDH1) positive cells. The aim of this study is to investigate the association between ALDH1 expression and clinicopathologic characteristics of invasive ductal carcinoma.
METHODS
We investigated breast cancer tissues for the prevalence of ALDH1+ tumor cells and their prognostic value. The present study included paraffin-embedded tissues of 70 patients with or without recurrences. We applied immunohistochemical staining for the detection of ALDH1+ cells. Analysis of the association of clinical outcomes and molecular subtype with marker status was conducted.
RESULTS
ALDH1+ and ALDH1- tumors were more frequent in triple-negative breast cancers and in luminal A breast cancers, respectively (p<0.01). ALDH1 expression was found to exert significant impact on disease free survival (DFS) (ALDH1+ vs. ALDH1-, 53.1+/-6.7 months vs. 79.2+/-4.7 months; p=0.03) and overall survival (OS) (ALDH1+ vs. ALDH1-, 68.5+/-4.7 months vs. 95.3+/-1.1 months; p<0.01). In triple-negative breast cancer (TNBC) patients, DFS and OS showed no statistical differences according to ALDH1 expression (ALDH1+ vs. ALDH1-, 45.3+/-9.4 months vs. 81.3+/-7.4 months, p=0.52; 69.0+/-7.5 months vs. 91.3+/-6.3 months, p=0.67). However, non-TNBC patients showed significant OS difference between ALDH1+ and ALDH1- tumors (ALDH1+ vs. ALDH1-, 77.6+/-3.6 months vs. 98.0+/-1.0 months; p=0.04) with no statistical difference of DFS (ALDH1+ vs. ALDH1-, 60.5+/-8.0 months vs. 81.8+/-4.6 months; p=0.27).
CONCLUSION
Our findings suggest that the expression of ALDH1 in breast cancer may be associated with TNBC and poor clinical outcomes. On the basis of our findings, we propose that ALDH1 expression in breast cancer could be correlated with poor prognosis, and may contribute to a more aggressive cancer phenotype.

Keyword

Aldehyde dehydrogenase; Breast neoplasms; Neoplastic stem cells

MeSH Terms

Aldehyde Dehydrogenase*
Breast
Breast Neoplasms*
Carcinoma, Ductal
Disease-Free Survival
Humans
Neoplastic Stem Cells
Phenobarbital
Phenotype
Prevalence
Prognosis
Recurrence
Stem Cells*
Triple Negative Breast Neoplasms
Aldehyde Dehydrogenase
Phenobarbital

Figure

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  Figure 1 Consolidated Standards of Reporting Trials diagram. IHC=immunohistochemistry.

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  Figure 2 Immunohistochemical staining of aldehyde dehydrogenase 1 (ALDH1) in tumor cells. (A) Diffuse staining was observed in cytoplasm and nucleus of cancer cells (positive reaction). (B) No ALDH1 staining was shown in cancer cells (negative reaction) (×400).

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  Figure 3 Survival curves between aldehyde dehydrogenase 1 (ALDH1)+ and ALDH1- patients. (A) Disease-free survival and (B) overall survival.

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  Figure 4 Survival curves between aldehyde dehydrogenase 1 (ALDH1)+ and ALDH1- patients according to molecular subtype. Disease-free survival in patients with (A) non-triple-negative breast cancer (TNBC) and (B) TNBC. Overall survival in patients with (C) non-TNBC and (D) TNBC.

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