Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers.
Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers.
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DOI：
10.1002/cjp2.6
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发表时间：
2015-01
期刊：
影响因子：
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通讯作者：
Bodvarsdottir SK
中科院分区：
文献类型：
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作者：
Aradottir M;Reynisdottir ST;Stefansson OA;Jonasson JG;Sverrisdottir A;Tryggvadottir L;Eyfjord JE;Bodvarsdottir SK
Aurora A激酶的过度表达已被证明在乳腺癌中具有预后价值。此前，我们发现乳腺癌患者中AURKA基因扩增与BRCA2突变之间存在显著的相关性。这项研究的目的是评估Aurora A过度表达对BRCA2突变携带者乳腺癌的预后影响。应用免疫组织化学方法检测107例BRCA2、999del5突变携带者和284例散发性乳腺癌组织芯片上Aurora A的表达。采用多因素Cox比例风险比回归模型，评估Aurora A核染色与临床指标和辅助治疗的预后价值。用TaqMan技术检测BRCA2突变肿瘤标本中BRCA2野生型等位基因缺失。所有的统计检验都是双面的。对乳腺癌特有生存率的多因素分析，包括增殖标志物和治疗，表明Aurora A核染色对BRCA2突变携带者的独立预后价值(危险比 = 7.06；95%可信区间 = 1.23-40.6；p = 0.028)。研究发现，BRCA2突变携带者乳腺癌特异性存活率低与肿瘤中Aurora A核表达和BRCA2野生型等位基因丢失显著相关(p <； 0.001)。多因素分析显示，AuroraA核染色阳性(危险比 = 10.09；95%可信区间 = 1.19~85.4，p = 0.034)和野生型等位基因缺失(危险比 = 9.63；95%可信区间 = 1.81~51.0，p = 0.008)对BRCA2突变携带者有独立的预后价值。Aurora A核表达被发现是BRCA2突变携带者的一个重要的预后标志，与临床参数和辅助治疗无关。我们的结论是，重视Aurora A靶向治疗可以提高BRCA2突变携带者和Aurora A阳性肿瘤散发性乳腺癌患者的治疗效益。
Overexpression of the Aurora A kinase has been shown to have prognostic value in breast cancer. Previously, we showed a significant association between AURKA gene amplification and BRCA2 mutation in breast cancer. The aim of this study was to assess the prognostic impact of Aurora A overexpression on breast cancer arising in BRCA2 mutation carriers. Aurora A expression was evaluated by immunohistochemistry on breast tumour tissue microarrays from 107 BRCA2 999del5 mutation carriers and 284 of sporadic origin. Prognostic value of Aurora A nuclear staining was estimated in relation to clinical markers and adjuvant treatment, using multivariate Cox's proportional hazards ratio regression model. BRCA2 wild‐type allele loss was measured by TaqMan in BRCA2 mutated tumour samples. All statistical tests were two sided. Multivariate analysis of breast cancer‐specific survival, including proliferative markers and treatment, indicated independent prognostic value of Aurora A nuclear staining for BRCA2 mutation carriers (hazards ratio = 7.06; 95% confidence interval = 1.23–40.6; p = 0.028). Poor breast cancer‐specific survival of BRCA2 mutation carriers was found to be significantly associated with combined Aurora A nuclear expression and BRCA2 wild type allele loss in tumours (p < 0.001). Multivariate analysis indicated independent prognostic value of both positive Aurora A nuclear staining (hazards ratio = 10.09; 95% confidence interval = 1.19–85.4, p = 0.034) and BRCA2 wild type allele loss (hazards ratio = 9.63; 95% confidence interval = 1.81–51.0, p = 0.008) for BRCA2 mutation carriers. Aurora A nuclear expression was found to be a significant prognostic marker for BRCA2 mutation carriers, independent of clinical parameters and adjuvant treatment. Our conclusion is that treatment benefits for BRCA2 mutation carriers and sporadic breast cancer patients with Aurora A positive tumours may be enhanced by giving attention to Aurora A targeted treatment.