{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:59:42Z","timestamp":1788872382332,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,9,30]],"date-time":"2014-09-30T00:00:00Z","timestamp":1412035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-10-1-0289"],"award-info":[{"award-number":["W81XWH-10-1-0289"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2014,12]]},"abstract":"Abstract<\/jats:title>\n \n The oviducts contain high\u2010grade serous cancer (\n HGSC<\/jats:styled-content>\n ) precursors (serous tubal intraepithelial neoplasia or\n STINs<\/jats:styled-content>\n ), which are \u03b3\u2010\n \n H2AX\n p<\/jats:sup>\n <\/jats:styled-content>\n \u2010 and\n \n TP53<\/jats:styled-content>\n <\/jats:italic>\n mutation\u2010positive. Although they express wild\u2010type p53, secretory cell outgrowths (\n SCOUTs<\/jats:styled-content>\n ) are associated with older age and serous cancer; moreover, both\n STINs<\/jats:styled-content>\n and\n SCOUTs<\/jats:styled-content>\n share a loss of\n PAX2<\/jats:styled-content>\n expression (\n \n PAX2\n n<\/jats:sup>\n <\/jats:styled-content>\n ). We evaluated\n PAX2<\/jats:styled-content>\n expression in proliferating adult and embryonic oviductal cells, normal mucosa,\n SCOUTs<\/jats:styled-content>\n , Walthard cell nests (\n WCNs<\/jats:styled-content>\n ),\n STINs<\/jats:styled-content>\n , and\n HGSCs<\/jats:styled-content>\n , and the expression of genes chosen empirically or from\n SCOUT<\/jats:styled-content>\n expression arrays. Clones generated\n in vitro<\/jats:italic>\n from embryonic gynaecological tract and adult Fallopian tube were Krt7\n p<\/jats:sup>\n \/\n \n PAX2\n n<\/jats:sup>\n <\/jats:styled-content>\n \/\n \n EZH2\n p<\/jats:sup>\n <\/jats:styled-content>\n and underwent ciliated (\n \n PAX2\n n<\/jats:sup>\n <\/jats:styled-content>\n \/\n \n EZH2\n n<\/jats:sup>\n <\/jats:styled-content>\n \/\n \n FOXJ1\n p<\/jats:sup>\n <\/jats:styled-content>\n ) and basal (Krt7\n n<\/jats:sup>\n \/\n \n EZH2\n n<\/jats:sup>\n <\/jats:styled-content>\n \/Krt5\n p<\/jats:sup>\n ) differentiation. Similarly, non\u2010ciliated cells in normal mucosa were\n \n PAX2\n p<\/jats:sup>\n <\/jats:styled-content>\n but became\n \n PAX2\n n<\/jats:sup>\n <\/jats:styled-content>\n in multi\u2010layered epithelium undergoing ciliated or basal (\n WCN<\/jats:styled-content>\n ) cell differentiation.\n \n PAX2\n n<\/jats:sup>\n SCOUTs\n <\/jats:styled-content>\n fell into two groups: type 1 were secretory or secretory\/ciliated with a \u2018tubal\u2019 phenotype and were\n \n ALDH1\n n<\/jats:sup>\n <\/jats:styled-content>\n and \u03b2\u2010catenin\n mem<\/jats:sup>\n (membraneous only). Type 2 displayed a columnar to pseudostratified (endometrioid) phenotype, with an\n \n EZH2\n p<\/jats:sup>\n <\/jats:styled-content>\n ,\n \n ALDH1\n p<\/jats:sup>\n <\/jats:styled-content>\n , \u03b2\u2010catenin\n nc<\/jats:sup>\n (nuclear and cytoplasmic), stathmin\n p<\/jats:sup>\n ,\n \n LEF1\n p<\/jats:sup>\n <\/jats:styled-content>\n ,\n \n RCN1\n p<\/jats:sup>\n <\/jats:styled-content>\n , and\n \n RUNX2\n p<\/jats:sup>\n <\/jats:styled-content>\n expression signature.\n STINs<\/jats:styled-content>\n and\n HGSCs<\/jats:styled-content>\n shared the type 1 immunophenotype of\n \n PAX2\n n<\/jats:sup>\n <\/jats:styled-content>\n ,\n \n ALDH1\n n<\/jats:sup>\n <\/jats:styled-content>\n , \u03b2\u2010catenin\n mem<\/jats:sup>\n , but highly expressed\n \n EZH2\n p<\/jats:sup>\n <\/jats:styled-content>\n ,\n \n LEF1\n p<\/jats:sup>\n <\/jats:styled-content>\n ,\n \n RCN1\n p<\/jats:sup>\n <\/jats:styled-content>\n , and stathmin\n p<\/jats:sup>\n . This study, for the first time, links\n \n PAX2\n n<\/jats:sup>\n <\/jats:styled-content>\n with proliferating fetal and adult oviductal cells undergoing basal and ciliated differentiation and shows that this expression state is maintained in\n SCOUTs<\/jats:styled-content>\n ,\n STINs<\/jats:styled-content>\n , and\n HGSCs<\/jats:styled-content>\n . All three entities can demonstrate a consistent perturbation of genes involved in potential tumour suppressor gene silencing (\n EZH2<\/jats:styled-content>\n ), transcriptional regulation (\n LEF1<\/jats:styled-content>\n ), regulation of differentiation (\n RUNX2<\/jats:styled-content>\n ), calcium binding (\n RCN1<\/jats:styled-content>\n ), and oncogenesis (stathmin). This shared expression signature between benign and neoplastic entities links normal progenitor cell expansion to abnormal and neoplastic outgrowth in the oviduct and exposes a common pathway that could be a target for early prevention. Copyright \u00a9 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd\n <\/jats:p>","DOI":"10.1002\/path.4417","type":"journal-article","created":{"date-parts":[[2014,8,6]],"date-time":"2014-08-06T10:02:38Z","timestamp":1407319358000},"page":"478-487","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["The\n PAX2<\/scp>\n \u2010null immunophenotype defines multiple lineages with common expression signatures in benign and neoplastic oviductal epithelium"],"prefix":"10.1002","volume":"234","author":[{"given":"Gang","family":"Ning","sequence":"first","affiliation":[{"name":"Jackson Laboratory for Genomic Medicine Farmington CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan G","family":"Bijron","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Utrecht Utrecht The 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