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Histopathology remains the gold standard, but differential diagnosis may be challenging. While absent in most epithelial, the expression of the adherens junction glycoprotein N\u2010cadherin is commonly restricted to neural and mesenchymal cells, or carcinoma cells that undergo the phenomenon of epithelial\u2010to\u2010mesenchymal transition (EMT). However, we recently established N\u2010 and E\u2010cadherin expression as hallmarks of normal hepatocytes and cholangiocytes, which are also preserved in HCC and iCCA. Therefore, we hypothesized that E\u2010 and\/or N\u2010cadherin may distinguish between carcinoma derived from the liver vs carcinoma of other origins. We comprehensively evaluated E\u2010 and N\u2010cadherin in 3359 different tumors in a multicenter study using immunohistochemistry and compared our results with previously published 882 cases of PLC, including 570 HCC and 312 iCCA. Most carcinomas showed strong positivity for E\u2010cadherin. Strong N\u2010cadherin positivity was present in HCC and iCCA. However, except for clear cell renal cell carcinoma (23.6% of cases) and thyroid cancer (29.2%), N\u2010cadherin was only in some instances faintly expressed in adenocarcinomas of the gastrointestinal tract (0%\u20130.5%), lung (7.1%), pancreas (3.9%), gynecological organs (0%\u20137.4%), breast (2.2%) as well as in urothelial (9.4%) and squamous cell carcinoma (0%\u20135.6%). As expected, N\u2010cadherin was detected in neuroendocrine tumors (25%\u201375%), malignant melanoma (46.2%) and malignant mesothelioma (41%). In conclusion, N\u2010cadherin is a useful marker for the distinction of PLC vs liver metastases of extrahepatic carcinomas (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.01).<\/jats:p>","DOI":"10.1002\/ijc.34836","type":"journal-article","created":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T04:52:06Z","timestamp":1705035126000},"page":"1857-1868","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["N\u2010cadherin: A diagnostic marker to help discriminate primary liver carcinomas from extrahepatic carcinomas"],"prefix":"10.1002","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9910-2186","authenticated-orcid":false,"given":"Tiemo S.","family":"Gerber","sequence":"first","affiliation":[{"name":"Institute of Pathology University Medicine, Johannes Gutenberg\u2010University  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk 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