High expression of stem cell marker ALDH1 is associated with reduced BRCA1 in invasive breast carcinomas

Asian Pac J Cancer Prev. 2012;13(6):2973-8. doi: 10.7314/apjcp.2012.13.6.2973.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aldehyde Dehydrogenase 1 Family
  • BRCA1 Protein / biosynthesis
  • BRCA1 Protein / genetics*
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Genotype
  • Humans
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics*
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells
  • Phenotype
  • Retinal Dehydrogenase / biosynthesis
  • Retinal Dehydrogenase / genetics*
  • Young Adult

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • Biomarkers, Tumor
  • Isoenzymes
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase