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Therefore, we conducted the present study to elucidate the clinicopathological and molecular characteristics of endometrial neuroendocrine carcinoma, as compared to conventional endometrial carcinoma, and to determine the origin of the former. We analyzed 22 endometrial neuroendocrine carcinomas and 22 conventional endometrial neoplasia cases with respect to clinical, histological and genetic features. Of these, 21\/22 neuroendocrine carcinoma cases were admixed carcinomas, with 15 admixed with endometrioid adenocarcinoma. Genetic analysis of hotspot mutations in 50 cancer\u2010related genes revealed that the neuroendocrine carcinoma group carried mutations in <jats:italic>PIK3CA<\/jats:italic> (12\/22 cases; 54%) and <jats:italic>PTEN<\/jats:italic> (8\/22 cases; 36%), commonly encountered in endometrioid adenocarcinoma. Comparative statistical analysis of neuroendocrine carcinoma and conventional endometrial neoplasia cases showed a significant trend only in <jats:italic>PIK3CA<\/jats:italic> mutation. Moreover, in six mixed\u2010type neuroendocrine carcinoma cases, macrodissection was used to separate the neuroendocrine carcinoma and endometrioid adenocarcinoma components for next\u2010generation sequencing, which revealed several mutations common among the two. These findings suggest that endometrial neuroendocrine carcinoma could originate from conventional endometrial neoplasia, especially endometrioid adenocarcinoma.<\/jats:p>","DOI":"10.1111\/pin.13108","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T18:12:19Z","timestamp":1621534339000},"page":"491-499","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Clinicopathological and molecular characteristics of endometrial neuroendocrine carcinomas reveal preexisting endometrial carcinoma origin"],"prefix":"10.1111","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1578-0081","authenticated-orcid":false,"given":"Kyoko","family":"Ono","sequence":"first","affiliation":[{"name":"Department of Pathology Kanagawa Cancer Center Kanagawa Japan"},{"name":"Department of Clinical Pathology Yokohama Municipal Citizen's Hospital Kanagawa Japan"},{"name":"Department of Molecular Pathology Yokohama City University Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rika","family":"Kasajima","sequence":"additional","affiliation":[{"name":"Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayoko","family":"Katayama","sequence":"additional","affiliation":[{"name":"Unit of Cancer Survivorship and Education, Kanagawa Cancer Center Research Institute Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Miyagi","sequence":"additional","affiliation":[{"name":"Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyuki","family":"Yokose","sequence":"additional","affiliation":[{"name":"Department of Pathology Kanagawa Cancer Center Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,20]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"ZainoR CarinelliSG EllensonLH et al.World Health Organization (WHO) Classification of Tumors of Female Reproductive Organs. 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