Elevated Aurora B expression contributes to chemoresistance and poor prognosis in breast cancer

Abstract

Aurora-B is a major kinase responsible for appropriate mitotic progression. Elevated expression of Aurora-B has been frequently associated with several types of cancer, including breast cancer. However, it is not clear whether the alteration contributes to tumor responses to therapies and prognosis. In this study, we conducted immunohistochemistry using antibodies against Aurora-B, S1981p-ATM, Ki67, and p53 in paraffin-embedded tumor tissues from 312 invasive breast cancer patients. The correlation between disease-free-survival (DFS) and Aurora-B expression was analyzed using the Kaplan-Meier method and log-rank test. A Cox proportional hazards regression analysis was used to determine whether Aurora-B was an independent prognostic factor for breast cancer. We found that Aurora-B expression was correlated with the proliferation index (P < 0.001) and p53 expression (P = 0.014) in breast cancer tissues. Further we found that Aurora-B expression was associated with lymph node metastasis (P = 0.002) and histological grade (P = 0.001). Multivariate analyses indicated that elevated Aurora-B expression predicted a poor survival. In a subgroup of patients that received neoadjuvant chemotherapy, we found that elevated Aurora-B contributed to chemoresistance (P = 0.011). In conclusion, elevated Aurora-B expression in breast cancer patients contributes to chemoresistance and predicts poor prognosis.

Keywords: Aurora-B; breast cancer; chemoresistance; prognosis.

Figure 1

Immunohistochemical study revealing representative images of invasive breast cancer and normal breast tissues with antibody of Aurora-B, nuclei with fine granular staining were counted, and (-/+) was < 5% of the cells stained, (++) was 5-10% of the cells stained, and (+++) was > 10% of the cells stained (A); and representative images of invasive breast cancer tissues stained with antibodies of Ki67, p53 and ATM-S1981p, they were scored as (-) = no positive cells, (+) = 1-10% of the cells stained, (++) = 11-50% of the cells stained, and (+++) = 51-100% of the cells stained as described previously [13] (B).

Figure 2

Kaplan-Meier survival curves of the 312 breast cancer patients with different expression levels of Aurora-B. Kaplan-Meier survival curves showed that higher expression of Aurora-B significantly correlated with the poor survival in these cases (P = 0.038).