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

Abstract

Background: 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. Methods: We examined 127 breast carcinomas for expression of ALDH1, using immunohistochemistry and correlated with clinicopathological parameters as well as the BRAC1 status. Results: 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. Conclusion: 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.