Gene expression profiling identifies molecular subtypes of inflammatory breast cancer
Gene expression profiling identifies molecular subtypes of inflammatory breast cancer
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DOI：
10.1158/0008-5472.can-04-4115
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发表时间：
2005-03-15
期刊：
影响因子：
11.2
通讯作者：
Birnbaum, D
中科院分区：
文献类型：
--
作者：
Bertucci, F;Finetti, P;Birnbaum, D
乳腺癌是一种异质性疾病。利用DNA微阵列获得的全面的基因表达谱揭示了以前无法区分的非炎症性乳腺癌(NIBC)亚型，与乳腺上皮生物学的不同特征有关，并与生存显著相关。炎症性乳腺癌(IBC)是一种罕见、特殊和侵袭性的疾病。在这里，我们调查了描述NIBC的五种分子亚型(管腔A和B、基底型、ERBB2过度表达和正常乳房样)是否也存在于IBC中。我们监测了83个乳腺组织样本中类似8,000个基因的RNA表达，其中包括37个IBC，44个NIBC和2个正常乳腺样本。在NIBC和IBC样本中，等级聚类确定了乳腺癌的五种亚型。这些亚型与以前研究中定义的亚型高度相似，并与相似的组织临床特征相关。用替代基因集和分析方法证实了该分类的稳健性，并在蛋白质水平上证实了结果。此外，我们还表明，我们最近报道的NIBC和IBC之间以及有和没有病理完全应答的IBC之间的基因表达差异在每个亚型中持续存在。我们的结果表明，定义NIBC分子亚型的表达特征也存在于IBC中。使用不同的患者系列和不同的微阵列平台获得的它们增强了对基于表达的分子分类学的信心，但也证明了它在乳腺癌中的普遍性，独立于特定的临床形式。
Breast cancer is a heterogeneous disease. Comprehensive gene expression profiles obtained using DNA microarrays have revealed previously indistinguishable subtypes of noninflammatory breast cancer (NIBC) related to different features of mammary epithelial biology and significantly associated with survival. Inflammatory breast cancer (IBC) is a rare, particular, and aggressive form of disease. Here we have investigated whether the five molecular subtypes described for NIBC (luminal A and B, basal, ERBB2 overexpressing, and normal breast-like) were also present in IBC. We monitored the RNA expression of similar to 8,000 genes in 83 breast tissue samples including 37 IBC, 44 NIBC, and 2 normal breast samples. Hierarchical clustering identified the five subtypes of breast cancer in both NIBC and IBC samples. These subtypes were highly similar to those defined in previous studies and associated with similar histoclinical features. The robustness of this classification was confirmed by the use of both alternative gene set and analysis method, and the results were corroborated at the protein level. Furthermore, we show that the differences in gene expression between NIBC and IBC and between IBC with and without pathologic complete response that we have recently reported persist in each subtype. Our results show that the expression signatures defining molecular subtypes of NIBC are also present in IBC. Obtained using different patient series and different microarray platforms, they reinforce confidence in the expression based molecular taxonomy but also give evidence for its universality in breast cancer, independently of a specific clinical form.