Association of aldehyde dehydrogenase 1 expression and biologically aggressive features in breast cancer
Abstract:
Aldehyde dehydrogenase 1 (ALDH1) has been regarded as a breast cancer stem cell marker. Several studies have reported that ALDH1 expression is associated with poor prognosis in breast cancer. We aimed, therefore, to determine the prognostic value of ALDH1 expression and its association with several biomarkers in breast cancer tissue using immunohistochemistry. Furthermore, we investigated the characteristics of and differences between cellular and stromal expression of ALDH1. We performed tissue microarray (TMA) analysis of 425 breast cancer tissue samples collected during surgery. Immunohistochemical staining was then performed to measure the expression of ALDH1 and other breast cancer biomarkers. Statistical analysis of the relationship between ALDH1 expression and clinicopathologic characteristics was performed for 390 TMA samples. We found that ALDH1 was expressed in 71 cases (18.2%) in the tumor cells and/or stroma. Of these cases, 38 (9.7%) showed ALDH1 expression in tumor cells and 38 (9.7%) showed ALDH1 expression in the stroma. ALDH1 expression was significantly associated with markers of a poor prognosis, such as young age, estrogen receptor negativity, progesterone receptor negativity, a high histological grade, and a high Ki-67 index. However, ALDH1 expression was not associated with p53, transforming growth factor-beta, Gli-1, YKL-40, or sonic hedgehog expression status. With regard to the expression site, the clinical characteristics did not differ between cases of cellular expression and those of stromal expression. However, ALDH1 expression in tumor cells was correlated with hormone receptor status, histological grade, molecular subtype, epidermal growth factor receptor expression status, and cytokeratin 5/6 expression status while stromal expression of ALDH1 was only correlated with hormone receptor status. Overall, these findings suggest that ALDH1 expression in tumor tissue is associated with a biologically aggressive phenotype.