Laas Enora, Ballester Marcos, Cortez Annie, Gonin Julie, Canlorbe Geoffroy, Daraï Emile, Graesslin Olivier
Service de Gynécologie-Obstétrique, Hôpital Tenon , AP-HP, Paris , France .
Gynecol Endocrinol. 2015 Apr;31(4):282-5. doi: 10.3109/09513590.2014.989981. Epub 2014 Dec 12.
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.
子宫内膜增生（EH）进展为子宫内膜样癌的风险范围从无不典型性的单纯EH（EHWA）的1%到不典型EH（AEH）的46.2%。区分这两种情况对于确定最佳治疗方案至关重要。由于术前诊断AEH可能困难，我们旨在建立免疫组化标志物簇以区分EHWA与AEH。我们研究了13种已知在子宫内膜病理中起作用的免疫组化标志物（类固醇受体、促/抗凋亡蛋白、金属蛋白酶（MMP）、金属蛋白酶组织抑制剂（TIMP）、CD44异构体）。使用监督聚类，我们确定了在区分EHWA与AEH中贡献最大的共表达蛋白簇。从39个组织样本（17个EHWA和22个AEH）中，我们发现了三个共表达蛋白簇：簇1包括两种蛋白（与EHWA相比，AEH中雌激素受体（ER）过表达和孕激素受体（PR）B低表达）；簇2：ER、PR A、MMP-2和TIMP-1过表达以及PR B和TIMP-2低表达；簇3：ER和MMP-7过表达以及PR B和TIMP-2低表达。使用免疫组化标志物的监督聚类可以准确区分AEH与EHWA。这种有前景的方法可能有助于改善EH的术前诊断。
