OP0015 Immunohistochemical study of stem cell markers ALDH1 and BRCA1 in breast cancer

Abstract

Background The BRCA1 gene is responsible for differentiation and maturation of mammary stem cells. Knockdown of this gene leads to evolution of a cell population with stem-cell-like characteristics (cancer stem cells), which in turn leads to the emergence of breast cancer, mostly with poor prognosis. This cell population can be highlighted by the stem cell marker ALDH1. This study focused on detecting a possible relation between BRCA1 mutation and emergence of a considerable population of ALDH1-positive cancer stem cells, and the correlation of this cell population with cancer prognostic factors. Methods Thirty cases of female breast cancer were evaluated immunohistochemically for the expression of both ALDH1 and BRCA1 in malignant epithelial cells, and correlation of ALDH1 expression with clinicopathological parameters such as age, positive family history of breast cancer, history of oral contraceptive pill intake, menopausal status, lactational history, tumour size, tumour type, tumour grade, and lymph node status. Findings Nine cases out of 30 (30%) showed positive cytoplasmic expression of ALDH1 in malignant epithelium. BRCA1 expression was positive in 18 cases (60%). Concomitant positive expression of both ALDH1 and BRCA1 was detected in two cases (11.1%). The relationships between positive ALDH1 expression and clinicopathological parameters were all non-significant. However, the relationship between positive ALDH1 expression, positive HER2, and negative ER and PR expression was highly significant. The relationship between positive BRCA1 expression and negative HER2 and ALDH1 expression was highly significant, and positive BRCA1 expression with positive ER and PR expression was highly significant, establishing protein expression profiles: (ALDH1–, BRCA1+, ER+, PR+, HER2–), which is correlated with good prognosis and outcome; and (ALDH1+, BRCA1–, ER–, PR, HER2+), which is correlated with worse prognosis and outcome. Interpretation The current study revealed a significant inverse correlation between expression of ALDH1 and BRCA1 and established phenotypes combining expression of ALDH1, BRCA1, ER, PR, and HER2, which correlate with prognosis and outcome. The importance of this and related studies emphasises the possible use of ALDH1 as a biomarker to screen family members at risk of BRCA1 mutations, and use as a prognostic marker owing to the fact that its expression correlates with basal type phenotype. In addition, ALDH1 might be a possible therapeutic target in breast cancer. All these are feasible provided we standardise methods of evaluation of immunohistochemical expression of ALDH1.