High Expression of Stem Cell Marker ALDH1 is Associated with Reduced BRCA1 in Invasive Breast Carcinomas

Zahra Madjd,Saadat Molanae,Mohsen Asadi-Lari,Babak Ramezani

doi:10.7314/apjcp.2012.13.6.2973

Abstract

Cancer stem cells (CSC) have been described in a variety of malignancies, including breast carcinomas. Among several markers, aldehyde dehydrogenase 1 (ALDH1) has been identified as reliable for breast cancer stem cells. Knockdown of BRCA1 in primary breast epithelial cells leads to an increase in cells expressing ALDH1. We examined 127 breast carcinomas for expression of ALDH1, using immunohistochemistry and correlated with clinicopathological parameters as well as the BRAC1 status. Comparing the results for both ALDH1 and BRCA1 expression showed a significant inverse association between the two, indicating that reduced BRCA1 was more often seen in breast cancer cells expressing ALDH1 (p-value = 0.044). A total of 24/110 (22%) of tumours displayed the ALDH1 + / BRCA1 -/low phenotype, which showed a trend for a relation with a high grade (p-value= 0.056). Cytoplasmic expression of ALDH1 was not correlated with tumour characteristics. Taken together, our findings suggest that increased ALDH1 is inversely correlated with decreased BRCA1 in a series of unselected breast carcinomas. Therefore, ALDH1 positive (cancer stem) cells with reduced BRCA1 phenotype may indicate a subset of patients for whom specific targeting of the CSC marker ALDH1 and more aggressive adjuvant treatment is appropriate.

Highlights

According to cancer stem cell (CSC) model, cancers are driven by a small subpopulation of stem cells with ability of self-renewal and give rise to multipotent progenitor cells that eventually differentiate into all cell types within the tumour (Visvader and Lindeman, 2008)
Taken together, our findings suggest that increased aldehyde dehydrogenase 1 (ALDH1) is inversely correlated with decreased BRCA1 in a series of unselected breast carcinomas
Expression of ALDH1 was seen in stromal cells as well as epithelial cells of breast tumours which is associated with good outcome, concluding that tumour environment play a crucial role in determining the prognostic impact of stem cells (Neumeister and Rimm, 2010; Resetkova et al, 2010)

Summary

Introduction

According to cancer stem cell (CSC) model, cancers are driven by a small subpopulation of stem cells with ability of self-renewal and give rise to multipotent progenitor cells that eventually differentiate into all cell types within the tumour (Visvader and Lindeman, 2008). Ginestier et al described that ALDH (aldehyde dehydrogenase) 1 may be a better marker for characterisation of breast cancer stem cells as fewer ALDH1+ tumour cells than CD44+ and CD24– tumour cells were required to produce tumours in immunodeficient mice. They found that ALDH1is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome (Balicki, 2007; Ginestier et al, 2007). It has been showed that knockdown of BRCA1 in primary breast epithelial cells leads to accumulation of cells expressing ALDH1 (Liu et al, 2008). ALDH1 positive (cancer stem) cells with reduced BRCA1 phenotype may indicate a subset of patients for whom specific targeting of the CSC marker ALDH1 and more aggressive adjuvant treatment is appropriate

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Results