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

Abstract

This study investigated the expression of ALDH1A1 and β-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 β-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 β-catenin, based on the survival status of breast cancer patients. Survival probabilities were estimated by the Kaplan-Meier method. ALDH1A1 expression was higher, but β-catenin showed no significant difference in breast cancer samples compared to controls. Compared with the membrane expression of β-catenin [β-catenin(m)], the cytoplasmic expression of β-catenin [β-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 β-catenin(c) breast cancer than in β-catenin(m) breast cancer (P=0.020). ALDH1A1(high) expression or β-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 β-catenin(c) was associated with lymph node metastasis, poor outcome, and resistance to cyclophosphamide treatment. β-catenin may regulate ALDH1A1 expression in a subtype of breast cancer with ALDH1A1(high) and β-catenin(c) expression. ALDH1A1(high) and β-catenin(c) expression may be used as a biomarker for predicting poor prognosis in breast cancer following cyclophosphamide treatment.