Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Histopathology. 2018 Aug;73(2):299-305. doi: 10.1111/his.13525. Epub 2018 May 31.
Dedifferentiated endometrial carcinomas (DDECs)/undifferentiated endometrial carcinomas (UECs) are aggressive endometrial cancers with frequent genomic inactivation of core components of switch/sucrose non-fermentable (SWI/SNF) complex proteins. Claudin-4, an epithelial intercellular tight junction protein, was recently found to be expressed in SWI/SNF-deficient undifferentiated carcinomas but not in SWI/SNF-deficient sarcomas. The aim of this study was to examine claudin-4 expression in UECs/DDECs and other high-grade uterine carcinomas.
We examined claudin-4 expression by immunohistochemistry (clone 3E2C1) on tissue microarrays that contained 44 UECs/DDECs (24 SWI/SNF-deficient), 50 carcinosarcomas, 164 grade 3 endometrioid carcinomas, 57 serous carcinomas, and 20 clear cell carcinomas. Tumours with <5% claudin-4 expression were considered to be negative. Nearly all SWI/SNF-deficient, and most SWI/SNF-proficient, UECs/DDECs showed a complete absence of claudin-4 expression in the undifferentiated component, whereas the differentiated component in DDECs showed consistent and diffuse claudin-4 expression. Only one SWI/SNF-deficient DDEC showed focal expression of claudin-4 in the undifferentiated component, as compared with diffuse expression in the corresponding differentiated component. Claudin-4 expression was consistently absent in the sarcomatous component of carcinosarcoma, and it was absent in 24% of grade 3 endometrioid carcinomas and serous carcinomas.
Claudin-4 expression can be absent or very focal in a subset of high-grade endometrial carcinomas, and is almost always absent in the undifferentiated components of SWI/SNF-deficient UECs/DDECs, despite the apparent epithelial origin in the case of DDECs. Therefore, claudin-4 expression cannot be used to infer mesenchymal or epithelial tumour origin in the endometrium. The consistent loss or down-regulation of claudin-4, a tight junction protein, in SWI/SNF-deficient UECs/DDECs further supports the undifferentiated nature of these tumours.
去分化子宫内膜癌（DDEC）/未分化子宫内膜癌（UEC）是具有侵袭性的子宫内膜癌，其核心成分的基因经常失活开关/蔗糖非发酵（SWI/SNF）复合物蛋白。 Claudin-4 是一种上皮细胞细胞间紧密连接蛋白，最近发现其在 SWI/SNF 缺陷型未分化癌中表达，但在 SWI/SNF 缺陷型肉瘤中不表达。本研究旨在研究 Claudin-4 在 UEC/DDEC 和其他高级别子宫癌中的表达。
我们通过组织微阵列免疫组化（克隆 3E2C1）检测 Claudin-4 的表达，该微阵列包含 44 例 UEC/DDEC（24 例 SWI/SNF 缺陷）、50 例癌肉瘤、164 例 3 级子宫内膜样癌、57 例浆液性癌和 20 例透明细胞癌。 Claudin-4 表达<5%的肿瘤被认为是阴性的。几乎所有的 SWI/SNF 缺陷型和大多数 SWI/SNF 功能正常型 UEC/DDEC 在未分化成分中均完全缺乏 Claudin-4 表达，而 DDEC 的分化成分则表现出一致的弥漫 Claudin-4 表达。与分化成分的弥漫表达相比，只有一例 SWI/SNF 缺陷型 DDEC 的未分化成分出现 Claudin-4 的局灶性表达。 Claudin-4 表达在癌肉瘤的肉瘤成分中始终缺失，在 24%的 3 级子宫内膜样癌和浆液性癌中缺失。
Claudin-4 表达在一部分高级别子宫内膜癌中可能缺失或非常局灶性，并且在 SWI/SNF 缺陷型 UEC/DDEC 的未分化成分中几乎总是缺失，尽管在 DDEC 的情况下上皮起源明显。因此， Claudin-4 表达不能用于推断子宫内膜中间质或上皮肿瘤的起源。 Claudin-4 是一种紧密连接蛋白，在 SWI/SNF 缺陷型 UEC/DDEC 中经常缺失或下调，进一步支持这些肿瘤的未分化性质。
