Molecular Anatomy of Breast Cancer Stroma and Its Prognostic Value in Estrogen Receptor-Positive and -Negative Cancers
Molecular Anatomy of Breast Cancer Stroma and Its Prognostic Value in Estrogen Receptor-Positive and -Negative Cancers
复制标题
DOI：
10.1200/jco.2009.27.2419
复制
发表时间：
2010-10-01
影响因子：
45.3
通讯作者：
Pusztai, Lajos
中科院分区：
文献类型：
--
作者：
Bianchini, Giampaolo;Qi, Yuan;Pusztai, Lajos
目的本研究的目的是鉴定乳腺癌基质中富含的基因，评估雌激素受体（ER）阳性和阴性癌症之间的基质基因表达差异，并分别确定它们在这两种乳腺癌亚型中的预后价值。方法我们比较了细针（基质贫乏）和芯针（基质丰富）对的基因表达谱 对 37 种癌症进行活检以确定基质相关基因。我们定义了间质元基因，并在 684 名未接受全身辅助治疗的淋巴结阴性患者和 259 名接受他莫昔芬治疗的患者中测试了它们的预后价值。结果我们鉴定了 293 个在核心活检中过表达的探针组；其中包括与免疫功能和细胞外基质成分相对应的五个高度共表达的基因簇（元基因）。这些基因显示 ER 阳性和 ER 阴性癌症之间的定量和定性差异。 B细胞/浆细胞宏基因在ER阳性高度增殖性癌症中显示出较强的预后价值，在ER阴性癌症中显示出较低的预后价值，而在ER阳性低增殖性癌症中则没有预后价值。与汇总预后数据集的最高三分位数相比，ER 阳性癌症中远处复发的风险比为 4.29（95% CI，2.04 至 9.01；P = 0.001），ER 阴性癌症中远处复发的风险比为 3.34（95% CI，1.60 至 6.97；P = 0.001）。这在包括常规变量和其他基因组预后评分的多变量分析中仍然很重要。由于 ER 阳性和 ER 阴性癌症之间的该元基因存在数量差异，因此这两个亚组适用不同的阈值。其他基质宏基因具有不一致的预后价值。结论在ER阴性和ER阳性高度增殖性癌症中，B细胞/浆细胞宏基因高表达的肿瘤子集具有良好的预后。
PurposeThe purpose of this study was to identify genes enriched in breast cancer stroma, assess the stromal gene expression differences between estrogen receptor (ER) -positive and -negative cancers, and separately determine their prognostic value in these two subtypes of breast cancers.MethodsWe compared gene expression profiles of pairs of fine-needle (stroma-poor) and core-needle (stroma-rich) biopsies from 37 cancers to identify stroma-associated genes. We defined stromal metagenes and tested their prognostic values in 684 node-negative patients who received no systemic adjuvant therapy and 259 tamoxifen-treated patients.ResultsWe identified 293 probe sets overexpressed in core biopsies; these included five highly coexpressed gene clusters (metagenes) corresponding to immune functions and extracellular matrix components. These genes showed quantitative and qualitative differences between ER-positive and ER-negative cancers. A B-cell/plasma cell metagene showed strong prognostic value in ER-positive highly proliferative cancers, a lesser prognostic value in ER-negative cancers, and no prognostic value in ER-positive cancers with low proliferation. The hazard ratio for distant relapse in the lowest compared with the highest tertile of the pooled prognostic data set was 4.29 (95% CI, 2.04 to 9.01; P = .001) in ER-positive cancers and 3.34 (95% CI, 1.60 to 6.97; P = .001) in ER-negative cancers. This remained significant in multivariate analysis including routine variables and other genomic prognostic scores. As a result of quantitative differences in this metagene between ER-positive and ER-negative cancers, different thresholds apply in the two subgroups. Other stromal metagenes had inconsistent prognostic value.ConclusionAmong ER-negative and ER-positive highly proliferative cancers, a subset of tumors with high expression of a B-cell/plasma cell metagene carries a favorable prognosis.