{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:53:54Z","timestamp":1785873234038,"version":"3.56.0"},"reference-count":16,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T00:00:00Z","timestamp":1480291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Immunohistochemistry for mismatch repair (<jats:styled-content style=\"fixed-case\">MMR<\/jats:styled-content>) proteins is being increasingly used to examine <jats:styled-content style=\"fixed-case\">MMR<\/jats:styled-content> status in tumours. The aim of the present article was to report the case of a colon cancer patient with Lynch syndrome who showed unusual cytoplasmic <jats:styled-content style=\"fixed-case\">MMR<\/jats:styled-content> protein localization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Histologically, the colon cancer was diagnosed as medullary carcinoma associated with prominent tumour\u2010infiltrating lymphocytes and a Crohn's\u2010like reaction. Immunohistochemistry revealed cytoplasmic and nuclear expression of <jats:styled-content style=\"fixed-case\">MSH<\/jats:styled-content>2 in non\u2010neoplastic cells, and exclusively cytoplasmic expression in tumour cells. MSH6 expression was nuclear in non\u2010neoplastic cells, but was lost in tumour cells. Nuclear expression of <jats:styled-content style=\"fixed-case\">MLH<\/jats:styled-content>1 and <jats:styled-content style=\"fixed-case\">PMS<\/jats:styled-content>2 was retained in both non\u2010neoplastic and tumour cells. The tumour was microsatellite instability\u2010high, which is indicative of defective <jats:styled-content style=\"fixed-case\">MMR<\/jats:styled-content> function. A subsequent germline mutation analysis identified a genomic deletion spanning the 3\u2032 region of <jats:italic>EPCAM<\/jats:italic> and the 5\u2032 region of <jats:italic>MSH2<\/jats:italic>, resulting in an in\u2010frame fusion of <jats:italic>EPCAM<\/jats:italic> and <jats:italic>MSH2<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The unusual cytoplasmic immunoreactivity of MSH2 was considered to be attributable to the non\u2010functional EPCAM\u2013MSH2 fusion product. The present case illustrates that not only loss of expression, but also abnormal localization, of <jats:styled-content style=\"fixed-case\">MMR<\/jats:styled-content> proteins is indicative of a defective <jats:styled-content style=\"fixed-case\">MMR<\/jats:styled-content> system.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13104","type":"journal-article","created":{"date-parts":[[2016,10,20]],"date-time":"2016-10-20T08:45:41Z","timestamp":1476953141000},"page":"664-669","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cytoplasmic MSH2 immunoreactivity in a patient with Lynch syndrome with an <i>EPCAM<\/i>\u2013<i>MSH2<\/i> fusion"],"prefix":"10.1111","volume":"70","author":[{"given":"Shigeki","family":"Sekine","sequence":"first","affiliation":[{"name":"Division of Pathology and Clinical Laboratories National Cancer Centre Hospital Tokyo Japan"},{"name":"Molecular Pathology Division National Cancer Centre Research 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