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However, the methylation and expression of these genes have not been validated in <jats:styled-content style=\"fixed-case\">EMPD<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aims to confirm the methylation and expression of <jats:styled-content style=\"fixed-case\">MMR<\/jats:styled-content> genes in <jats:styled-content style=\"fixed-case\">EMPD<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immunohistochemical (<jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>) staining detection and Methylation\u2010specific <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">MSP<\/jats:styled-content>) were used to analyse <jats:styled-content style=\"fixed-case\">MLH<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">MSH<\/jats:styled-content>2, <jats:styled-content style=\"fixed-case\">MSH<\/jats:styled-content>6 and <jats:styled-content style=\"fixed-case\">PMS<\/jats:styled-content>2 proteins\u2019 expression and promoters\u2019 methylation in 57 <jats:styled-content style=\"fixed-case\">EMMD<\/jats:styled-content> samples, and pyro\u2010sequence was used to find highly methylated CpG sites in <jats:italic><jats:styled-content style=\"fixed-case\">MSH<\/jats:styled-content>2<\/jats:italic> promoter.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Immunohistochemical detection displayed reduced expression of <jats:styled-content style=\"fixed-case\">MSH<\/jats:styled-content>2 in 38.6% <jats:styled-content style=\"fixed-case\">EMPD<\/jats:styled-content> cases but normal expression of <jats:styled-content style=\"fixed-case\">MLH<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">MSH<\/jats:styled-content>6 and <jats:styled-content style=\"fixed-case\">PMS<\/jats:styled-content>2 in all tumour tissues. Hypermethylation also was found in the promoter of <jats:italic><jats:styled-content style=\"fixed-case\">MSH<\/jats:styled-content>2<\/jats:italic> but not in other <jats:styled-content style=\"fixed-case\">MMR<\/jats:styled-content> genes. Pyrosequencing of <jats:italic><jats:styled-content style=\"fixed-case\">MSH<\/jats:styled-content>2<\/jats:italic> promoter showed CpG6 (\u201087) and CpG3 (\u201098) were the most common two methylated CpG dinucleotides. There is a significant correlation between reduced <jats:styled-content style=\"fixed-case\">MSH<\/jats:styled-content>2 expression and <jats:italic><jats:styled-content style=\"fixed-case\">MSH<\/jats:styled-content>2<\/jats:italic> methylation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Reduced <jats:styled-content style=\"fixed-case\">MSH<\/jats:styled-content>2 expression and hypermethylation in this gene promoter were common genetic changes in <jats:styled-content style=\"fixed-case\">EMPD<\/jats:styled-content>, which expands our understanding of the role of <jats:styled-content style=\"fixed-case\">MMR<\/jats:styled-content> function in this skin cancer.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.15404","type":"journal-article","created":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T06:16:39Z","timestamp":1550643399000},"page":"874-879","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Methylation and expression analysis of mismatch repair genes in extramammary Paget's disease"],"prefix":"10.1111","volume":"33","author":[{"given":"Z.","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Huashan Hospital Fudan University Shanghai P. 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