The fibromatosis signature defines a robust stromal response in breast carcinoma
The fibromatosis signature defines a robust stromal response in breast carcinoma
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DOI：
10.1038/labinvest.2008.31
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发表时间：
2008-06-01
影响因子：
5
通讯作者：
West, Robert B.
中科院分区：
文献类型：
--
作者：
Beck, Andrew H.;Espinosa, Inigo;West, Robert B.
乳腺癌是一种异质性疾病，基质基因和蛋白质表达模式对疾病的生物学和临床异质性的影响知之甚少。我们以前证明，两种软组织肿瘤（韧带样型纤维瘤病（DTF）和孤立性纤维瘤）的基因表达模式的评价，可用于确定不同的乳腺癌间质反应模式。在目前的研究中，我们检查了从四个不同机构获得的另外四个数据集，其中包含来自总共561名乳腺癌患者的基因表达数据。我们确定了66个DTF相关基因的核心组，这些基因在25-35%的乳腺癌中一致协调表达。由DTF核心基因的高水平协调表达定义的乳腺癌倾向于较低级别，表达雌激素受体，并且在四个数据集中显示出显著更长的生存期。使用从总共745例患者中获得的存档乳腺癌标本的多个组织微阵列，我们证明了乳腺癌的一个子集显示DTF核心蛋白在肿瘤微环境中由基质细胞协调表达。我们评估了一个单一的DTF核心蛋白（DTF）的蛋白表达的组织微阵列与临床结果的数据，并证明了乳腺癌与强大的基质蛋白表达的DTF显示出增加生存的趋势。我们的数据表明，DTF核心基因集是一个强大的描述了一个独特的基质反应，是与改善乳腺癌患者的临床结果。
Breast cancer is a heterogeneous disease, and the influence of stromal gene and protein expression patterns on the biological and clinical heterogeneity of the disease is poorly understood. We previously demonstrated that evaluation of the gene expression patterns of two soft-tissue tumors (desmoid-type fibromatosis (DTF) and solitary fibrous tumor) could be used to identify distinct stromal reaction patterns in breast carcinoma. In the current study, we examined four additional data sets obtained from four different institutions and containing gene expression data from a total of 561 breast cancer patients. We identified a core set of 66 DTF-associated genes that were consistently coordinately expressed in a subset of 25-35% of breast cancers. Breast carcinomas defined by high levels of coordinated expression of DTF core genes tend to be lower grade, express estrogen receptor, and show significantly longer survival across the four data sets. Using multiple tissue microarrays of archival breast cancer specimens obtained from a total of 745 patients, we demonstrated that a subset of breast cancers show coordinate expression of DTF core proteins by stromal cells in the tumor microenvironment. We evaluated the protein expression of a single DTF core protein (SPARC) on a tissue microarray with clinical outcome data and demonstrated that breast cancers with strong stromal protein expression of SPARC show a trend for increased survival. Our data demonstrate that the DTF core gene set is a robust descriptor of a distinct stromal response that is associated with improved clinical outcome in breast cancer patients.