Aurora Kinase A (AURKA) is an independent predictor of recurrence in breast ductal carcinoma in situ (DCIS)

Abstract

Background: Current clinical and pathological parameters are important predictors of recurrence in breast ductal carcinoma in situ (DCIS) but they are insufficient to reflect its molecular heterogeneity. Biological characterisation has the potential for individualising therapy for DCIS. Aurora Kinase A (AURKA), located on 20q13.2, shows copy number alteration in DCIS and is a key regulator of cell cycle progression. High expression of AURKA is associated with poor outcome in invasive breast cancer (IBC), however it is not confirmed in the pre-invasive stage. This study aims to assess the role of AURKA in DCIS behaviour. Methods: 776 consecutive DCIS patients treated in Nottingham between 1990 and 2012 were prepared as tissue microarrays. Patients' clinical information, management and follow-up data were retrospectively collected. The expression of AURKA was assessed immunohistochemically and assessed with clinicopathological parameters. Results: Pure DCIS lesions showed higher expression of AURKA compared to lesions associated with IBC (p=3x10-8). In pure DCIS tumours, high nuclear AURKA expression was associated with features of aggressiveness including high nuclear grade (p=0.04) and presence of comedo necrosis (p=0.03). Univariate outcome analysis showed positive association with development of local invasive recurrence (p=6x10-6). Multivariate analyses indicate that independent predictors of DCIS recurrence are high AURKA expression (p=8x10-5, HR=5.5 and 95%CI: 2.4-12.9), larger DCIS size and high nuclear grade. Conclusions: AURKA expression predicts local recurrence in DCIS patients and is potentially useful in prognostic stratification of DCIS patients for management decisions.