High survivin mRNA expression is a predictor of poor prognosis in breast cancer: a comparative study at the mRNA and protein level
High survivin mRNA expression is a predictor of poor prognosis in breast cancer: a comparative study at the mRNA and protein level
复制标题
DOI：
10.1007/s12282-012-0403-9
复制
发表时间：
2012
期刊：
影响因子：
4
通讯作者：
Chunsen Xu;M. Yamamoto-Ibusuki;Yutaka Yamamoto;Satoko Yamamoto;Saori Fujiwara;K. Murakami;Y. Okumura
中科院分区：
文献类型：
--
作者：
Chunsen Xu;M. Yamamoto-Ibusuki;Yutaka Yamamoto;Satoko Yamamoto;Saori Fujiwara;K. Murakami;Y. Okumura
研究背景Survivin在乳腺癌的发生发展中起关键作用。然而，它与乳腺癌患者的预后相关性长期以来一直是一个有争议的问题。本研究旨在检测Survivin在一系列乳腺癌组织中的表达及其在预测临床预后中的作用。方法采用实时定量RT-PCR方法检测245例女性浸润性乳腺癌和13例乳腺导管原位癌石蜡包埋组织中Survivin基因的表达。此外，237例浸润性乳腺癌的肿瘤可用于免疫组织化学(IHC)。结果RT-qPCR结果显示Survivin基因高表达与乳腺癌的核级别高、腋窝淋巴结阳性、激素受体状态阴性、Her2扩增阳性、Ki67标记指数高、有血管侵犯密切相关。在Cox比例回归模型分析中，Survivin mRNA是影响无复发生存期(RFS)、无远处复发生存期(DRFS)和乳腺癌特异性生存期(BCS)的显著单变量参数，也是影响RFS、DRFS和BCS的显著多变量参数。在激素受体(HR)阳性/Her2阴性亚型病例中，Survivin mRNA的表达也是DRFS的独立预测因素。免疫组织化学显示，Survivin的高表达与肿瘤细胞的mRNA水平无关，也不具有预后价值。结论Survivin的高表达是整个队列和HR阳性/Her2阴性亚型患者预后不良的独立标志，而Survivin蛋白的高表达不是预后不良的独立标志。这些发现表明，在验证Survivin对乳腺癌患者预后的意义方面，RT-qPCR可以提供比IHC更可靠的数据。
BackgroundSurvivin plays a key role in the initiation and progression of breast cancer. However, its prognostic relevance to breast cancer patients has long been a matter of debate. The purpose of this study was to examine the expression of survivin and its role in predicting clinical outcome in a series of human breast cancer cases both at the mRNA and protein level.MethodsFormalin-fixed paraffin-embedded tumor tissues from 245 female patients with invasive breast cancer and 13 patients with ductal carcinoma in situ were examined for survivin mRNA by quantitative real-time RT-PCR (RT-qPCR). In addition, 237 of these tumors with invasive breast cancer were available for immunohistochemistry (IHC). The relationship between survivin status and clinicopathological characteristics and prognosis was evaluated.ResultsRT-qPCR revealed that high levels of survivin mRNA were strongly associated with high nuclear grade, positive axillary lymph nodes, negative hormone receptor status, positive Her2 amplification, higher Ki67 labeling index, and presence of vascular invasion. In the Cox proportional regression model analysis, survivin mRNA was shown to be a significant univariate parameter for relapse-free survival (RFS), distant relapse-free survival (DRFS), and breast cancer-specific survival (BCSS) as well as a significant multivariate parameter for RFS, DRFS, and BCSS. In hormone receptor (HR)-positive/Her2-negative subtype cases, survivin mRNA expression was also an independent predictor in terms of DRFS. Immunohistochemically, positive staining was seen in the cytoplasm and/or nucleus of cancer cells, although this did not correlate with the mRNA level, and harbored no prognostic value.ConclusionsHigh mRNA expression of survivin was an independent marker of poor prognosis both in the entire cohort and in the HR-positive/Her2-negative subtype, whereas the protein expression of survivin was not. These findings suggest that RT-qPCR can provide more reliable data than IHC in validating the prognostic significance of survivin for breast cancer patients.