Molecular diversity in ductal carcinoma in situ (DCIS) and early invasive breast cancer
Molecular diversity in ductal carcinoma in situ (DCIS) and early invasive breast cancer
复制标题
DOI：
10.1016/j.molonc.2010.06.007
复制
发表时间：
2010-08-01
影响因子：
6.6
通讯作者：
Warnberg, Fredrik
中科院分区：
文献类型：
--
作者：
Muggerud, Aslaug Aamodt;Hallett, Michael;Warnberg, Fredrik
导管原位癌（DCIS）是一种非侵袭性乳腺癌，其中局限于导管的细胞表现出非典型表型。一些DCIS病变被认为会迅速转变为浸润性导管癌（IDC），而另一些则保持不变。现有的DCIS分类系统无法识别转移到IDC的病变。我们使用Agilent全人类基因组寡核苷酸微阵列44 k研究了31例纯DCIS，36例纯浸润性癌症和42例混合诊断（浸润性癌症与原位成分）的基因表达模式。还包括6个正常乳腺组织样本作为对照。qRT-PCR用于验证。所有DCIS和浸润性样本可被分类为浸润性乳腺癌定义的“内在”分子亚型。层次聚类建立了样本组的内在亚型，而不是诊断。我们观察到高组织学级别DOS中转录组的异质性，并确定了一个独特的亚组，其中包含31个DCIS样本中的7个，其基因表达特征更类似于晚期肿瘤。通过逻辑回归鉴定一组与分级、ER状态和HER 2状态无关的基因，该逻辑回归将样本单变量分类为属于该独特的DCIS亚组。单一标志物的qRT-PCR清楚地将该DCIS亚组与其他DCIS分开，并且包含来自几种组织病理学和内在分子亚型的样品。区分这两种类型DCIS的基因表明了与微环境重组相关的几个过程。这为识别具有和不具有侵入性特征的DCIS病变提出了有趣的可能性，这可能用于临床评估女性的进展风险，并导致改善管理，从而避免目前对患者的过度治疗和治疗不足。(C)2010年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer where cells restricted to the ducts exhibit an atypical phenotype. Some DCIS lesions are believed to rapidly transit to invasive ductal carcinomas (IDCs), while others remain unchanged. Existing classification systems for DCIS fail to identify those lesions that transit to IDC. We studied gene expression patterns of 31 pure DCIS, 36 pure invasive cancers and 42 cases of mixed diagnosis (invasive cancer with an in situ component) using Agilent Whole Human Genome Oligo Microarrays 44k. Six normal breast tissue samples were also included as controls. qRT-PCR was used for validation. All DCIS and invasive samples could be classified into the "intrinsic" molecular subtypes defined for invasive breast cancer. Hierarchical clustering establishes that samples group by intrinsic subtype, and not by diagnosis. We observed heterogeneity in the transcriptomes among DOS of high histological grade and identified a distinct subgroup containing seven of the 31 DCIS samples with gene expression characteristics more similar to advanced tumours. A set of genes independent of grade, ER-status and HER2-status was identified by logistic regression that univariately classified a sample as belonging to this distinct DCIS subgroup. qRT-PCR of single markers clearly separated this DCIS subgroup from the other DCIS, and contains samples from several histopathological and intrinsic molecular subtypes. The genes that differentiate between these two types of DCIS suggest several processes related to the re-organisation of the microenvironment. This raises interesting possibilities for identification of DCIS lesions both with and without invasive characteristics, which potentially could be used in clinical assessment of a woman's risk of progression, and lead to improved management that would avoid the current over- and under-treatment of patients. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.