Progression of ductal carcinoma in situ to invasive breast cancer is associated with gene expression programs of EMT and myoepithelia
Progression of ductal carcinoma in situ to invasive breast cancer is associated with gene expression programs of EMT and myoepithelia
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DOI：
10.1007/s10549-011-1894-3
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发表时间：
2012-06-01
影响因子：
3.8
通讯作者：
Witkiewicz, Agnieszka K.
中科院分区：
文献类型：
--
作者：
Knudsen, Erik S.;Ertel, Adam;Witkiewicz, Agnieszka K.
导管原位癌(DCIS)是一种可导致浸润性乳腺癌(IBC)的前驱病变。已经提出，病变的性质和肿瘤的微环境在IBC的进展中起着关键作用。在这里，激光捕获显微解剖组织从纯DCIS和纯IBC中被用来确定与疾病进展相关的上皮室或间质室的关键基因表达谱。每个组织都有不同的基因表达谱，DCIS/IBC分类器在多个独立的数据集中准确区分DCIS和IBC。然而，与其他描述DCIS与侵袭性疾病相关的研究相反，我们发现最显著的基因表达变化发生在上皮室而不是间质。特别是，与上皮向间充质转化相关的基因和肌上皮细胞特异性基因在浸润性癌中比单纯DCIS丰富。转录水平的这种变化与乳腺癌的所有亚型都有关，但尤其表明ER阴性乳腺癌的预后不佳。总之，这些研究表明，与浸润性表型相关的病变特异性基因表达的差异在DCIS向浸润性乳腺癌的发展过程中尤其相关。
Ductal carcinoma in situ (DCIS) is a precursor lesion that can gives rise to invasive breast cancer (IBC). It has been proposed that both the nature of the lesion and the tumor microenvironment play key roles in progression to IBC. Here, laser capture microdissected tissue from pure DCIS and pure IBC were employed to define key gene expression profiles in either the epithelial or stromal compartment associated with disease progression. Each tissue had distinct gene expression profiles, and a DCIS/IBC classifier accurately distinguished DCIS versus IBC in multiple independent data sets. However, contrary to other studies that profiled DCIS associated with invasive disease, we found that the most significant alterations in gene expression were observed in the epithelial compartment rather than in the stroma. In particular, genes associated with epithelial-to-mesenchymal transition and myoepithelial cell-specific genes were enriched in invasive cancer relative to pure DCIS. Such alterations in transcript levels were associated with all subtypes of breast cancer, but were particularly indicative of poor outcome in ER-negative breast cancer. Together, these studies indicate that lesion-specific differences in gene expression associated with invasive phenotype are particularly relevant in the progression of DCIS to invasive breast cancer.