Tumor gene expression and prognosis in breast cancer patients with 10 or more positive lymph nodes
Tumor gene expression and prognosis in breast cancer patients with 10 or more positive lymph nodes
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DOI：
10.1158/1078-0432.ccr-05-0735
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发表时间：
2005-12-15
影响因子：
11.5
通讯作者：
Shak, S
中科院分区：
文献类型：
--
作者：
Cobleigh, MA;Tabesh, B;Shak, S
目的：这项研究，沿着与其他两项研究，是为了开发21基因复发评分测定（Oncotype DX），该测定在随后的独立研究中得到验证，并用于辅助雌激素受体（ER）阳性、淋巴结阴性乳腺癌患者的化疗决策。从石蜡块中提取RNA，并使用逆转录- PCR（RT-PCR）定量203个候选基因的表达。截至2002年8月，77%的患者有远处复发或乳腺癌死亡。单因素考克斯分析显示HER 2/免疫组化、受累淋巴结数、孕激素受体（PR）/免疫组化（%细胞）和ER/免疫组化（%细胞）与无远处复发生存率（DRFS）显著相关。单因素考克斯分析确定了22个与DRFS相关的基因。对于HER 2衔接子GRB 7和巨噬细胞标志物CD 68，较高的表达与较短的DRFS相关。肿瘤蛋白p53结合蛋白2（TP 53 BP 2）和ER轴基因PR和Bcl 2的高表达与较长的DRFS相关。多变量方法，包括逐步变量选择和自举的考克斯比例风险回归模型，确定了几个基因，包括TP 53 BP 2和Bcl 2，作为DRFS.Conclusion的显着预测因子：肿瘤基因表达谱档案组织，一些超过20岁，提供了显着的信息，即使在10个或更多的节点的患者的远处复发的风险。
Purpose: This study, along with two others, was done to develop the 21 -gene Recurrence Score assay (Oncotype DX) that was validated in a subsequent independent study and is used to aid decision making about chemotherapy in estrogen receptor (ER) - positive, node-negative breast cancer patients.Experimental Design: Patients with >= 10 nodes diagnosed from 1979 to 1999 were identified. RNA was extracted from paraffin blocks, and expression of 203 candidate genes was quantified using reverse transcription- PCR (RT-PCR).Results: Seventy-eight patients were studied. As of August 2002,77% of patients had distant recurrence or breast cancer death. Univariate Cox analysis of clinical and immunohistochemistry variables indicated that HER 2/ immunohistochemistry, number of involved nodes, progesterone receptor (PR)/immunohistochemistry (%cells), and ER/immunohistochemistry (%cells) were signif- icantly associated with distant recurrence-free survival (DRFS). Univariate Cox analysis identified 22 genes associated with DRFS. Higher expression correlated with shorter DRFS for the HER2 adaptor GRB7 and the macrophage marker CD68. Higher expression correlated with longer DRFS for tumor protein p53-binding protein 2 (TP53BP2) and the ER axis genes PR and Bcl2. Multivariate methods, including stepwise variable selection and bootstrap resampling of the Cox proportional hazards regression model, identified several genes, including TP53BP2 and Bcl2, as significant predictors of DRFS.Conclusion: Tumor gene expression profiles of archival tissues, some more than 20 years old, provide significant information about risk of distant recurrence even among patients with 10 or more nodes.