Aurora Kinase A Is an Independent Predictor of Invasive Recurrence in Breast Ductal Carcinoma in situ

Abstract

<b><i>Introduction:</i></b> Aurora Kinase A (AURKA/STK15) has a role in centrosome duplication and is a regulator of mitotic cell proliferation. It is over-expressed in breast cancer and other cancers, however; its role in ductal carcinoma in situ (DCIS) remains to be defined. This study aims to characterize AURKA protein expression in DCIS and evaluate its prognostic significance. <b><i>Methods:</i></b> AURKA was assessed immunohistochemically in a large well-characterized cohort of DCIS (<i>n</i> = 776 pure DCIS and 239 DCIS associated with invasive breast cancer [DCIS-mixed]) with long-term follow-up data (median = 105 months) and basic molecular characterization. <b><i>Results:</i></b> High AURKA expression was observed in 15% of DCIS cases and was associated with features of aggressiveness including larger tumour size, high nuclear grade, hormone receptor negativity, HER2 positivity, and high Ki67 proliferation index. AURKA expression was higher in DCIS associated with invasive breast cancer than in pure DCIS (<i>p</i> < 0.0001). In the DCIS-mixed cohort, the invasive component showed higher AURKA expression than the DCIS component (<i>p</i> < 0.0001). Outcome analysis revealed that AURKA was a predictor of invasive recurrence (<i>p</i> = 0.002). <b><i>Conclusion:</i></b> High AURKA expression is associated with poor prognosis in DCIS and might be a potential marker to predict DCIS progression to invasive disease.

Research progress on the relationship between AURKA and tumorigenesis: the neglected nuclear function of AURKA

“…Given that AURKA has been found to be aberrantly expressed in a variety of tumors since its discovery, it was identified as an oncogene [ 12 ]. High levels of AURKA are associated with malignant tumor proliferation [ 13 ], invasion and metastasis [ 14 ], splicing disorders [ 15 ], epithelial-mesenchymal transformation [ 16 ], radioresistance [ 17 ], chemotherapy resistance [ 18 ] and immune escape [ 19 ]. Therefore, small molecule kinase inhibitors targeting AURKA have been successively developed.…”