Protein kinase CK2α subunit over-expression correlates with metastatic risk in breast carcinomas: Quantitative immunohistochemistry in tissue microarrays
Protein kinase CK2α subunit over-expression correlates with metastatic risk in breast carcinomas: Quantitative immunohistochemistry in tissue microarrays
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DOI：
10.1016/j.ejca.2010.11.028
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发表时间：
2011-03-01
影响因子：
8.4
通讯作者：
Charpin, Colette
中科院分区：
文献类型：
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作者：
Giusiano, Sophie;Cachet, Claude;Charpin, Colette
背景：CK2α是一种信号分子，参与实体瘤进展的主要事件。本研究的目的是评估乳腺癌中 CK2 α 免疫组织化学表达的预后意义。方法：使用高通量密度测定法定量测量 33 种生物标志物的免疫组织化学表达，并使用单变量和多变量分析对数字化显微组织微阵列图像进行评估，与 1000 例乳腺癌的临床结果相关。结果：在单变量分析中，CK2 α 是显着的预后指标（p < 0.001）。此外，多变量模型允许选择 33 种生物标志物的最佳组合，以通过逻辑回归预测患者的结果。高度预测转移风险的九个标记特征，与 SHARP-2、STAT1、eIF4E、pmap-KAPk-2、pAKT、caveolin、VEGF、FGF-1 和 CK2 α 相关，可以对 82.32% 的患者进行良好分类（特异性 81.59%，敏感性 92.55%，ROC 曲线下面积 0.939）。重要的是，在淋巴结阴性的患者子集中，发现 11 种标记物具有更多 (86%) 临床相关性，可预测不良预后。结论：乳腺癌中强定量 CK2 α 免疫组织化学表达是预后不良的重要指标。此外，包括 CK2 α 在内的 11 种标记物的免疫组织化学特征准确地 (86%) 将淋巴结阴性患者分为良好和不良结果子集。我们的结果表明，CK2 α 评估与关键下游 CK2 靶点可能是识别远处转移高风险患者的有用工具，并且 CK2 可以被视为潜在特异性治疗的相关靶点。 (C) 2010 Elsevier Ltd. 保留所有权利。
Background: CK2 alpha is a signalling molecule that participates in major events in solid tumour progression. The aim of this study was to evaluate the prognostic significance of the immunohistochemical expression of CK2 alpha in breast carcinomas.Methods: Quantitative measurements of immunohistochemical expression of 33 biomarkers using high-throughput densitometry, assessed on digitised microscopic tissue microarray images were correlated with clinical outcome in 1000 breast carcinomas using univariate and multivariate analyses.Results: In univariate analysis, CK2 alpha was a significant prognostic indicator (p < 0.001). Moreover, a multivariable model allowed the selection of the best combination of the 33 biomarkers to predict patients' outcome through logistic regression. A nine-marker signature highly predictive of metastatic risk, associating SHARP-2, STAT1, eIF4E, pmap-KAPk-2, pAKT, caveolin, VEGF, FGF-1 and CK2 alpha permitted to classify well 82.32% of patients (specificity 81.59%, sensitivity 92.55%, area under ROC curve 0.939). Importantly, in a node negative subset of patients an even more (86%) clinically relevant association of eleven markers was found predictive of poor outcome.Conclusion: A strong quantitative CK2 alpha immunohistochemical expression in breast carcinomas is individually a significant indicator of poor prognosis. Moreover, an immunohistochemical signature of 11 markers including CK2 alpha accurately (86%) well classifies node negative patients in good and poor outcome subsets. Our results suggest that CK2 alpha evaluation together with key downstream CK2 targets might be a useful tool to identify patients at high risk of distant metastases and that CK2 can be considered as a relevant target for potential specific therapy. (C) 2010 Elsevier Ltd. All rights reserved.