Mucinous carcinoma of the breast is genomically distinct from invasive ductal carcinomas of no special type
Mucinous carcinoma of the breast is genomically distinct from invasive ductal carcinomas of no special type
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DOI：
10.1002/path.2763
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发表时间：
2010-11-01
影响因子：
7.3
通讯作者：
Reis-Filho, Jorge S.
中科院分区：
文献类型：
--
作者：
Lacroix-Triki, Magali;Suarez, Paula H.;Reis-Filho, Jorge S.
粘液癌是一种罕见的实体，占所有乳腺癌的 2%，已显示出与非特殊类型的浸润性导管癌 (IDC-NST) 不同的基因表达谱。在这里，我们定义了这种特殊类型乳腺癌特征的基因组畸变，并研究了粘液癌是否可能构成与 IDC-NST 不同的基因组实体。使用针对雌激素受体 (ER)、黄体酮受体、HER2、Ki67、细胞周期蛋白 D1、皮质素、Bcl-2、p53、E-钙粘蛋白、基础标记物、神经内分泌标记物和 WT1 的抗体，通过免疫组织化学方法对 35 例纯性乳腺癌和 11 例混合性粘液性乳腺癌进行评估。对 15 个纯粘液癌和 30 个级别和 ER 匹配的 IDC-NST 进行显微解剖，并进行基于高分辨率微阵列的比较基因组杂交 (aCGH)。此外，对七种混合粘液癌的不同成分分别进行显微解剖并进行 aCGH。纯粘液癌一致表达 ER (100%)，缺乏 HER2 表达 (97.1%)，并且表现出相对较低水平的遗传不稳定性。无监督的分层聚类分析显示，纯粘液癌是同质的，并且优先聚集在一起，与 IDC-NST 分开。与级别和 ER 匹配的 IDC-NST 相比，它们较少出现 1q 和 16p 增益以及 16q 和 22q 丢失，并且没有纯粘液癌同时表现出 1q 增益和 16q 丢失，这是低级别 IDC-NST 的标志性遗传特征。最后，除了一种混合性粘液癌之外，所有的两种成分都显示出相似的遗传畸变模式，并且在无监督聚类分析中优先与纯粘液癌聚类在一起。我们的结果表明，粘液癌在基因水平上比 IDC-NST 更具有同质性。混合性粘液性肿瘤的两种成分在分子水平上与纯粘液性癌非常相似，这表明混合性粘液性癌可能最好归类为粘液性癌的变体，而不是 IDC-NST 的变体。版权所有 (C) 2010 大不列颠及爱尔兰病理学会。由约翰·威利父子有限公司出版
Mucinous carcinomas are a rare entity accounting for up to 2% of all breast cancers, which have been shown to display a gene expression profile distinct from that of invasive ductal carcinomas of no special type (IDC-NSTs). Here, we have defined the genomic aberrations that are characteristic of this special type of breast cancer and have investigated whether mucinous carcinomas might constitute a genomic entity distinct from IDC-NSTs. Thirty-five pure and 11 mixed mucinous breast carcinomas were assessed by immunohistochemistry using antibodies against oestrogen receptor (ER), progesterone receptor, HER2, Ki67, cyclin D1, cortactin, Bcl-2, p53, E-cadherin, basal markers, neuroendocrine markers, and WT1. Fifteen pure mucinous carcinomas and 30 grade- and ER-matched IDC-NSTs were microdissected and subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). In addition, the distinct components of seven mixed mucinous carcinomas were microdissected separately and subjected to aCGH. Pure mucinous carcinomas consistently expressed ER (100%), lacked HER2 expression (97.1%), and showed a relatively low level of genetic instability. Unsupervised hierarchical cluster analysis revealed that pure mucinous carcinomas were homogeneous and preferentially clustered together, separately from IDC-NSTs. They less frequently harboured gains of 1q and 16p and losses of 16q and 22q than grade- and ER-matched IDC-NSTs, and no pure mucinous carcinoma displayed concurrent 1q gain and 16q loss, a hallmark genetic feature of low-grade IDC-NSTs. Finally, both components of all but one mixed mucinous carcinoma displayed similar patterns of genetic aberrations and preferentially clustered together with pure mucinous carcinomas on unsupervised clustering analysis. Our results demonstrate that mucinous carcinomas are more homogeneous between themselves at the genetic level than IDC-NSTs. Both components of mixed mucinous tumours are remarkably similar at the molecular level to pure mucinous cancers, suggesting that mixed mucinous carcinomas may be best classified as variants of mucinous cancers rather than of IDC-NSTs. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.