Combined expression of aldehyde dehydrogenase 1A1 and β-catenin is associated with lymph node metastasis and poor survival in breast cancer patients following cyclophosphamide treatment

This study investigated the expression of ALDH1A1 and beta-catenin in breast cancer patients, and analyzed the correlation of their combined expression with clinicopathological features, chemotherapeutic responses, and prognosis of breast cancer patients. In total 276 human breast cancer tissues and 80 benign hyperplasia tissues were included. The expression of ALDH1A1 and beta-catenin was examined using tissue microarray-based immunohistochemistry. ROC curve analysis was performed to determine an optimal cut-off score for the expression of ALDH1A1 and beta-catenin, based on the survival status of breast cancer patients. Survival probabilities were estimated by the Kaplan-Meier method. ALDH1A1 expression was higher, but beta-catenin showed no significant difference in breast cancer samples compared to controls. Compared with the membrane expression of beta-catenin [beta-catenin(m)], the cytoplasmic expression of beta-catenin [beta-catenin(c)] occurred significantly more frequently in breast cancer with the high expression of ALDH1A1 [ALDH1A1(high)] than in breast cancer with the low expression of ALDH1A1 [ALDH1A1(low)] (P=0.014). The expression level of ALDH1A was significantly higher in beta-catenin(c) breast cancer than in beta-catenin(m) breast cancer (P=0.020). ALDH1A1(high) expression or beta-catenin(c) expression alone was associated with lymph node metastasis, and worse clinical outcome in breast cancer patients, especially in patients receiving cyclophosphamide treatment. Combined expression of ALDH1A1(high) and beta-catenin(c) was associated with lymph node metastasis, poor outcome, and resistance to cyclophosphamide treatment. beta-catenin may regulate ALDH1A1 expression in a subtype of breast cancer with ALDH1A1(high) and beta-catenin(c) expression. ALDH1A1(high) and beta-catenin(c) expression may be used as a biomarker for predicting poor prognosis in breast cancer following cyclophosphamide treatment.