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Supervised clustering of immunohistochemical markers to distinguish atypical and non-atypical endometrial hyperplasia

机译:免疫组织化学标志物的监督聚类,以区分非典型和非非典型子宫内膜增生

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摘要

The risk of endometrial hyperplasia (EH) progressing into endometrioid endometrial cancer ranges from 1% for simple EH without atypia (EHWA) to 46.2% for atypical EH (AEH). Differentiation between both entities is crucial to determine optimal management. As preoperative diagnosis of AEH can be difficult, we aimed to establish clusters of immunohistochemical markers to distinguish EHWA from AEH. We studied 13 immunohistochemical markers (steroid receptors, pro/anti-apoptotic proteins, metalloproteinases (MMP), tissue inhibitor of metalloproteinase (TIMP), CD44 isoforms) known for their role in endometrial pathology. Using supervised clustering, we determined clusters of co-expressed proteins which contributed the most in differentiating EHWA from AEH. From 39 tissue samples (17 EHWA and 22 AEH), we found three clusters of co-expressed proteins: Cluster 1 included two proteins (over-expression of estrogen receptor (ER) and under-expression of progesterone receptor (PR) B in AEH compared to EHWA); Cluster 2: an ER, PR A, MMP-2 and TIMP-1 over-expression and a PR B and TIMP-2 under-expression; Cluster 3: over-expression of ER and MMP-7 and under-expression of PR B and TIMP-2. AEH can be accurately distinguished from EHWA using a supervised clustering of immunohistochemical markers. This promising approach could be useful to improve the preoperative diagnosis of EH.
机译:子宫内膜增生(EH)的风险进展到子宫内膜子宫内膜癌为1%的简单EH,无典型的eh(ehwa)为46.2%,适用于非典型eh(aeh)。两个实体之间的差异对于确定最佳管理至关重要。由于术前诊断AEH可以困难,我们旨在建立免疫组织化学标记的簇,以区分EEH。我们研究了13种免疫组织化学标记物(类固醇受体,Pro /抗凋亡蛋白,金属蛋白酶(MMP),含金属蛋白酶(TIMP),CD44同种型的组织抑制剂,其在子宫内膜病理学中的作用。使用监督聚类,我们确定了联合表达蛋白质的簇,这些蛋白质贡献了差异化艾震的eeh。从39个组织样品(17 ehwa和22 aeh),我们发现三种共同表达蛋白质:簇1包括两种蛋白质(雌激素受体(ER)的过表达,并且在aeh中的孕酮受体(pr)b的表达。与ehwa相比);群集2:ER,PR A,MMP-2和TIMP-1过表达和PR B和TIMP-2欠表达;群集3:ER和MMP-7的过表达以及PR B和TIMP-2的表达。可以使用免疫组织化学标记的监督聚类来精确地区分AEH。这种有希望的方法可用于改善eh的术前诊断。

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