极光激酶A是乳腺导管原位癌侵袭性复发的独立预测因子。

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

作者信息

Miligy Islam M, Toss Michael S, Gorringe Kylie L, Ellis Ian O, Green Andrew R, Rakha Emad A

机构信息

Division of Cancer and Stem Cells, Nottingham Breast Cancer Research Centre, School of Medicine, Nottingham City Hospital, The University of Nottingham, Nottingham, UK,

Histopathology Department, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt,

出版信息

Pathobiology. 2022;89(6):382-392. doi: 10.1159/000522244. Epub 2022 May 9.

DOI:10.1159/000522244

PMID:35533650

Abstract

INTRODUCTION

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.

METHODS

AURKA was assessed immunohistochemically in a large well-characterized cohort of DCIS (n = 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.

RESULTS

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 (p < 0.0001). In the DCIS-mixed cohort, the invasive component showed higher AURKA expression than the DCIS component (p < 0.0001). Outcome analysis revealed that AURKA was a predictor of invasive recurrence (p = 0.002).

CONCLUSION

High AURKA expression is associated with poor prognosis in DCIS and might be a potential marker to predict DCIS progression to invasive disease.

摘要

引言

极光激酶A（AURKA/STK15）在中心体复制中起作用，是有丝分裂细胞增殖的调节因子。然而，它在乳腺癌和其他癌症中过度表达，其在导管原位癌（DCIS）中的作用仍有待确定。本研究旨在描述DCIS中AURKA蛋白的表达特征，并评估其预后意义。

方法

采用免疫组织化学方法对一大组特征明确的DCIS队列（n = 776例纯DCIS和239例与浸润性乳腺癌相关的DCIS [DCIS-混合]）进行AURKA评估，并提供长期随访数据（中位数 = 105个月）和基本分子特征。

结果

在15%的DCIS病例中观察到AURKA高表达，且与侵袭性特征相关，包括肿瘤体积较大、核分级高、激素受体阴性、HER2阳性和高Ki67增殖指数。与浸润性乳腺癌相关的DCIS中AURKA表达高于纯DCIS（p < 0.0001）。在DCIS-混合队列中，浸润成分的AURKA表达高于DCIS成分（p < 0.0001）。预后分析显示，AURKA是侵袭性复发的预测因子（p = 0.002）。