Estrogen receptor co-activator (AIB1) protein expression by automated quantitative analysis (AQUA) in a breast cancer tissue microarray and association with patient outcome
Estrogen receptor co-activator (AIB1) protein expression by automated quantitative analysis (AQUA) in a breast cancer tissue microarray and association with patient outcome
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DOI：
10.1007/s10549-008-0063-9
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发表时间：
2009-05-01
影响因子：
3.8
通讯作者：
Rimm, David L.
中科院分区：
文献类型：
--
作者：
Harigopal, Malini;Heymann, Jonas;Rimm, David L.
目的乳腺癌扩增蛋白（Amplified in breast cancer，AIB 1或SRC-3）是一种雌激素受体共调节蛋白，与转录中介因子2（transformation intermediate factor 2，TIF 2）、核受体共抑制因子（nuclear receptor co-repressor，NCoR）等共激活因子共同参与雌激素信号通路和雌激素调节的肿瘤进展。我们研究了乳腺组织芯片（TMA）中AIB 1、TIF 2和NCoR蛋白表达的预后意义，并研究了共调节蛋白与预后生物标志物雌激素（ER）、孕激素（PR）和HER 2/neu的关系以及共调节蛋白之间的关系。方法：应用AQUA软件对670例乳腺癌组织中的TMA进行AIBI、TIF 2和NCoR的荧光免疫组织化学染色。测试结果：使用考克斯单变量生存分析，AIB 1高表达与患者预后不良相关（P = 0.002），而TIF 2（P = 0.376）和NCoR（P = 0.12）无相关性。当按淋巴结或ER状态进行亚分类时，AIB 1在淋巴结阳性和ER阳性亚群中不具有预后性。然而，在ER阴性和淋巴结阴性亚群中，AIB 1高表达与患者预后不良相关（分别为P = 0.02和P = 0.007）。多变量分析显示AIB 1与生存率保持独立相关性（P = 0.028）。AIB 1与ER、PR状态及其他因子（TIF 2、NCoR）呈正相关，与HER 2/neu状态无相关性。结论：AIB 1高表达预示着较差的总生存率，提示AIB 1可能在乳腺癌发生中起关键作用。
Purpose Amplified in breast cancer (AIB1 or SRC-3) is an estrogen receptor coregulatory protein that together with other co-activators like transcription intermediary factor 2 (TIF2) and nuclear receptor co-repressor (NCoR), is implicated in estrogen signaling pathway and estrogen regulated tumor progression. We investigated the prognostic significance of AIB1, TIF2 & NCoR protein expression breast tissue microarray (TMA), and studied the relationship of coregulatory proteins to prognostic biomarkers like estrogen (ER), progesterone (PR) & HER2/neu and between coregulatory proteins. Methods: AIBI, TIF2 & NCoR were studied by fluorescent immunohistochemical staining of a TMA with 670 breast cancer specimens, using AQUA software. Result: Using Cox univariate survival analyses, high AIB1 expression was associated with poor patient outcome (P = 0.002), while no association was noted for TIF2 (P = 0.376) & NCoR (P = 0.12). When subclassified by nodal or ER status, AIB1 was not prognostic in the node positive and ER positive subsets. However, in the ER negative and node negative subsets, high AIB1 expression was associated with poor patient outcome (P = 0.02 and P = 0.007 respectively). AIB1 retained its independent association with survival by multivariate analyses (P = 0.028). There was significant positive correlation between AIB1 and ER and PR status and with other cofators (TIF2 and NCoR) but not with HER2/neu status. Conclusion: High AIB1 expression was predictive of worse overall survival in our study, suggesting that AIB1 may be critical in breast carcinogenesis.