Expression of Aurora A (but not Aurora B) is predictive of survival in breast cancer.
Expression of Aurora A (but not Aurora B) is predictive of survival in breast cancer.
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DOI：
10.1158/1078-0432.ccr-07-5268
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发表时间：
2008-07-15
期刊：
影响因子：
--
通讯作者：
Kluger Y
中科院分区：
文献类型：
--
作者：
Nadler Y;Camp RL;Schwartz C;Rimm DL;Kluger HM;Kluger Y
细胞周期介质Aurora A和B是目前临床开发的药物的靶点。与乳腺癌的其他靶向治疗一样，对治疗的反应可能与肿瘤中的靶向表达相关。因此，我们评估了Aurora A和B在乳腺肿瘤中的表达，并研究了其与临床/病理变量的相关性。采用我们的自动化定量分析方法，使用包含638例随访15年的患者的原发标本的组织微阵列来评估Aurora A和B的表达;我们使用细胞角蛋白在阵列斑点内将像素定义为乳腺癌（肿瘤掩模），并使用Cy 5缀合抗体测量掩模内的Aurora A和B表达。Aurora A和B在原发性乳腺肿瘤中的表达是可变的。高Aurora A表达与生存率降低密切相关（P = 0.0005）。在多变量分析中，它仍然是一个独立的预后指标。Aurora A高表达与高细胞核分级、HER-2/neu和孕酮受体高表达相关。Aurora B表达与生存率无关。Aurora A表达定义了存活率降低的患者群体，而Aurora B表达则没有，这表明Aurora A可能是乳腺癌的首选药物靶点。Aurora A在早期乳腺癌中的表达可以识别需要更积极或靶向治疗的患者子集。需要进行前瞻性研究以确认Aurora A的预后作用以及Aurora A表达在接受Aurora A抑制剂治疗的患者中的预测作用。
The cell cycle mediators Aurora A and B are targets of drugs currently in clinical development. As with other targeted therapies in breast cancer, response to therapy might be associated with target expression in tumors. We therefore assessed expression of Aurora A and B in breast tumors and studied associations with clinical/pathologic variables. Tissue microarrays containing primary specimens from 638 patients with 15-year follow-up were employed to assess expression of Aurora A and B using our automated quantitative analysis method; we used cytokeratin to define pixels as breast cancer (tumor mask) within the array spot and measured Aurora A and B expression within the mask using Cy5-conjugated antibodies. Aurora A and B expression was variable in primary breast tumors. High Aurora A expression was strongly associated with decreased survival (P = 0.0005). On multivariable analysis, it remained an independent prognostic marker. High Aurora A expression was associated with high nuclear grade and high HER-2/neu and progesterone receptor expression. Aurora B expression was not associated with survival. Aurora A expression defines a population of patients with decreased survival, whereas Aurora B expression does not, suggesting that Aurora A might be the preferred drug target in breast cancer. Aurora A expression in early-stage breast cancer may identify a subset of patients requiring more aggressive or pathway-targeted treatment. Prospective studies are needed to confirm the prognostic role of Aurora A as well as the predictive role of Aurora A expression in patients treated with Aurora A inhibitors.