A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays
A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays
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DOI：
10.1002/ijc.24177
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发表时间：
2009-05-01
影响因子：
6.4
通讯作者：
Garcia, Stephane
中科院分区：
文献类型：
--
作者：
Charpin, Colette;Secq, Veronique;Garcia, Stephane
在构建组织微阵列后，对 1,200 例乳腺癌进行了定量免疫细胞化学分析。通过单变量对数等级检验（平均随访，79 个月），使用图像分析设备和特定软件的定量评分，评估了总共 42 个标志物的预后意义。获得了 924 名患者的完整数据，42 种标志物中有 27 种被证明是重要的预后指标。通过逻辑回归对这 27 个标记物进行分析显示，其中 18 个（cMet、CD44v6、FAK、moesin、caveolin、c-Kit、CK14、CD10、P21、P27、pMAPK、pSTAT3、sSTAT1、SHARP2、FYN、ER、PgR 和 c-erb 132），排除 ER、PgR 和 c-erb B2 时为 15 个，分别对疾病结果的预测率为 80.52% 和 78.9%。在目前的实践中，对 4 微米厚的固定组织切片进行免疫细胞化学测定很容易处理，并且具有成本效益。通过计算机辅助设备根据数字化显微图像对免疫沉淀物进行定量光密度测量，可以在肿瘤内进行标准化的高通量“原位”分子分析。结论是，由于在固定肿瘤样本的石蜡切片上进行，因此这 15 个标记的免疫组织化学特征适合当前实践。并且可用于选择需要更积极治疗的患者，因为该特征大约 80% 可以预测不良的临床结果。此外，签名中包含的标记物可能表明肿瘤对当前化疗的反应性或为特定疗法提出新靶点。 (C) 2008 Wiley-Liss, Inc.
Quantitative immunocytochemical assays of 1,200 breast carcinomas were assessed after construction of tissue microarrays. A total of 42 markers were evaluated for prognostic significance by univariate log rank test (mean follow-up, 79 months), using quantitative scoring by an image analysis device and specific software. Complete data were obtained fir 924 patients, for whom 27 of the 42 markers proved to be significant prognostic indicators. Analysis of these 27 markers by logistic regression showed that 18 (cMet, CD44v6, FAK, moesin, caveolin, c-Kit, CK14, CD10, P21, P27, pMAPK, pSTAT3, sTAT1, SHARP2, FYN, ER, PgR and c-erb 132), and 15 when ER, PgR and c-erb B2 were excluded, were 80.52% and 78.9% predictive of disease outcome, respectively. The immunocytochemical assays on 4 micron thick sections of fixed tissue are easy to handle in current practice and are cost-effective. Quantitative densitometric measurement of immunoprecipitates by computer-assisted devices from digitized microscopic images allows standardized high-throughput "in situ" molecular profiling within tumors. It is concluded that this 15 marker immunohistochemical signature is suitable for current practice, since performed on paraffin sections of fixed tumor samples. and can be used to select patients needing more aggressive therapy, since this signature is about 80% predictive of poor clinical outcome. Also, the markers included in the signature may he indicative of tumor responsiveness to current chemotherapy or suggest new targets for specific therapies. (C) 2008 Wiley-Liss, Inc.