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Frequent loss of claudin‐4 expression in dedifferentiated and undifferentiated endometrial carcinomas
Author(s) -
TessierCloutier Basile,
Soslow Robert A,
Stewart Colin J R,
Köbel Martin,
Lee ChengHan
Publication year - 2018
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13525
Subject(s) - claudin , carcinosarcoma , serous fluid , immunohistochemistry , pathology , tissue microarray , biology , carcinoma , cancer research , tight junction , medicine , microbiology and biotechnology
Aims Dedifferentiated endometrial carcinomas ( DDEC s)/undifferentiated endometrial carcinomas ( UEC s) 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 UEC s/ DDEC s and other high‐grade uterine carcinomas. Methods and results We examined claudin‐4 expression by immunohistochemistry (clone 3E2C1) on tissue microarrays that contained 44 UEC s/ DDEC s (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, UEC s/ DDEC s showed a complete absence of claudin‐4 expression in the undifferentiated component, whereas the differentiated component in DDEC s 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. Conclusion 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 UEC s/ DDEC s, despite the apparent epithelial origin in the case of DDEC s. 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 UEC s/ DDEC s further supports the undifferentiated nature of these tumours.