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 breastcarcinomas. Among several markers, aldehyde dehydrogenase 1 (ALDH1) has been identified as reliable for breastcancer stem cells. Knockdown of BRCA1 in primary breast epithelial cells leads to an increase in cells expressingALDH1.
Methods: We examined 127 breast carcinomas for expression of ALDH1, using immunohistochemistryand correlated with clinicopathological parameters as well as the BRAC1 status.
Results: Comparing the resultsfor both ALDH1 and BRCA1 expression showed a significant inverse association between the two, indicatingthat reduced BRCA1 was more often seen in breast cancer cells expressing ALDH1 (p-value = 0.044). A totalof 24/110 (22%) of tumours displayed the ALDH1 + / BRCA1 -/low phenotype, which showed a trend for arelation with a high grade (p-value= 0.056). Cytoplasmic expression of ALDH1 was not correlated with tumourcharacteristics.
Conclusion: Taken together, our findings suggest that increased ALDH1 is inversely correlatedwith 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 CSCmarker ALDH1 and more aggressive adjuvant treatment is appropriate.

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