Clear cell and endometrioid carcinomas: are their differences attributable to distinct cells of origin?
Clear cell and endometrioid carcinomas: are their differences attributable to distinct cells of origin?
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DOI：
10.1002/path.4934
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发表时间：
2017-09-01
影响因子：
7.3
通讯作者：
Huntsman, David G.
中科院分区：
文献类型：
--
作者：
Cochrane, Dawn R.;Tessier-Cloutier, Basile;Huntsman, David G.
子宫内膜上皮被认为是异位和子宫内膜异位症衍生的透明细胞癌和子宫内膜样癌的起源组织。我们先前假设这些癌之间的形态学、生物学和临床差异是由于组织型特异性突变。尽管一些突变和基因组景观特征更有可能在其中一种组织型中发现，但我们无法确定一种类型的突变只存在于一种组织型中，而不存在于另一种组织型中。这种基因组差异的缺失使我们产生了另一种假设，即这些癌症可能起源于子宫内膜组织内不同的细胞，而正是细胞环境导致了它们的差异。在蛋白质组学筛选中，我们确定了胱氨酸γ裂解酶（CTH）作为透明细胞癌的标记物，因为它在卵巢和子宫内膜的透明细胞癌中表达水平很高。在目前的研究中，我们分析了正常的苗勒氏组织，发现CTH在子宫内膜（异位子宫内膜和子宫内膜异位症）和输卵管的纤毛细胞中表达。然后我们证明其他纤毛细胞标记物在透明细胞癌中表达，而子宫内膜分泌细胞标记物在子宫内膜样癌中表达。在三维类器官培养系统中，干细胞被刺激分化为分泌细胞和纤毛细胞的混合物，分泌细胞和纤毛细胞的差异染色是相同的。这些数据表明，子宫内膜样癌来源于分泌细胞系，而透明细胞癌来源于纤毛细胞系，或与纤毛细胞系有相似之处。版权所有2017英国和爱尔兰病理学会。约翰·威利父子有限公司出版。
Endometrial epithelium is the presumed tissue of origin for both eutopic and endometriosis-derived clear cell and endometrioid carcinomas. We had previously hypothesized that the morphological, biological and clinical differences between these carcinomas are due to histotype-specific mutations. Although some mutations and genomic landscape features are more likely to be found in one of these histotypes, we were not able to identify a single class of mutations that was exclusively present in one histotype and not the other. This lack of genomic differences led us to an alternative hypothesis that these cancers could arise from distinct cells of origin within endometrial tissue, and that it is the cellular context that accounts for their differences. In a proteomic screen, we identified cystathionine gamma-lyase (CTH) as a marker for clear cell carcinoma, as it is expressed at high levels in clear cell carcinomas of the ovary and endometrium. In the current study, we analysed normal Mullerian tissues, and found that CTH is expressed in ciliated cells of endometrium (both eutopic endometrium and endometriosis) and fallopian tubes. We then demonstrated that other ciliated cell markers are expressed in clear cell carcinomas, whereas endometrial secretory cell markers are expressed in endometrioid carcinomas. The same differential staining of secretory and ciliated cells was demonstrable in a three-dimensional organoid culture system, in which stem cells were stimulated to differentiate into an admixture of secretory and ciliated cells. These data suggest that endometrioid carcinomas are derived from cells of the secretory cell lineage, whereas clear cell carcinomas are derived from, or have similarities to, cells of the ciliated cell lineage. Copyright (C) 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.