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Open Access Highly Accessed Research article

Age determines the prognostic role of the cancer stem cell marker aldehyde dehydrogenase-1 in breast cancer

J Sven D Mieog1, Esther M de Kruijf1, Esther Bastiaannet12, Peter JK Kuppen1, Anita Sajet1, Anton JM de Craen2, Vincent THBM Smit3, Cornelis JH van de Velde1 and Gerrit-Jan Liefers1*

Author Affiliations

1 Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands

2 Department of Gerontology & Geriatrics, Leiden University Medical Center, Leiden, The Netherlands

3 Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands

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BMC Cancer 2012, 12:42  doi:10.1186/1471-2407-12-42

Published: 26 January 2012

Abstract

Background

The purpose of this study was to compare the expression and the prognostic effect of the breast cancer stem cell marker aldehyde dehydrogenase-1 (ALDH1) in young and elderly breast cancer patients.

Methods

The study population (N = 574) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1994. Median follow-up was 17.9 years (range: 0.1 to 23.5). Tissue microarray slides were immunohistochemically stained for ALDH1 expression and quantified by two independent observers who were blinded to clinical outcome. Assessment of the prognostic effect of ALDH1 expression was stratified according to age and systemic treatment.

Results

Complete lack of expression of ALDH1 was found in 40% of tumors. With increasing age more tumors showed complete absence of ALDH1 expression (P < .001). In patients aged > 65 years, ALDH1 status was not associated with any clinical outcome. Conversely, in patients aged < 65 years, ALDH1 positivity was an independent risk factor of worse outcome for relapse free period (hazard ratio = 1.71 (95% CI, 1.09 to 2.68); P = .021) and relative survival (relative excess risks of death = 2.36 (95% CI, 1.22 to 3.68); P = .016). Ten-year relative survival risk was 57% in ALDH1-positive patients compared to 83% in ALDH1-negative patients.

Conclusion

ALDH1 expression and its prognostic effect are age-dependent. Our results support the hypothesis that breast cancer biology is different in elderly patients compared to their younger counterparts and emphasizes the importance of taking into consideration age-specific interactions in breast cancer research.

Keywords:
Breast cancer; Age; ALDH1; Prognostic factor Part of this work has been presented at the American Association for Cancer Research (AACR) Annual Meeting 2011