Frequent loss of claudin‐4 expression in dedifferentiated and undifferentiated endometrial carcinomas
Frequent loss of claudin‐4 expression in dedifferentiated and undifferentiated endometrial carcinomas
AimsDedifferentiated 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.Methods and resultsWe 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.ConclusionClaudin‐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.
- Vancouver Coastal Health Canada
- Alberta Health Services Canada
- Vancouver General Hospital Canada
- University of Western Australia Australia
- Memorial Sloan Kettering Cancer Center United States
Biomarkers, Tumor, Humans, Female, Claudin-4, Endometrial Neoplasms
Biomarkers, Tumor, Humans, Female, Claudin-4, Endometrial Neoplasms
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