{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:02:58Z","timestamp":1792652578134,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"am","delay-in-days":301,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T00:00:00Z","timestamp":1538006400000},"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":["OC130500OC160444"],"award-info":[{"award-number":["OC130500OC160444"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["OC160444"],"award-info":[{"award-number":["OC160444"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["OC130500"],"award-info":[{"award-number":["OC130500"]}],"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":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The distal Fallopian tube is a site of origin for many \u2018ovarian\u2019 high\u2010grade serous carcinomas (HGSCs) with intraepithelial carcinomas (STICs) that share identical\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations with metastatic tumors.\n                    <jats:italic>TP53<\/jats:italic>\n                    mutation\u2010positive early serous proliferations (ESPs) comprise a spectrum including p53 signatures and serous tubal intraepithelial lesions (STILs) and are not considered malignant; however, ESPs are often the only abnormality found in Fallopian tubes of women with metastatic HGSC. The purpose of this study was to determine if a relationship exists between\n                    <jats:italic>isolated<\/jats:italic>\n                    ESPs and concurrent metastatic HGSCs in the absence of STIC. Fallopian tubes from 32 HGSCs without a co\u2010existing STIC\/HGSC in the endosalpinx were exhaustively sectioned. The presence of either STIC\/HGSC or ESP in the endosalpinx was documented and DNA from tissues containing ESPs, concurrent HGSC, and control epithelia were interrogated for\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations by targeted amplicon\u2010based sequencing with average coverage reads &gt;4000 across DNA replicate samples. Serial sectioning revealed a previously unrecognized STIC\/HGSC in 3 of 32 (9.3%) and ESPs in 13 (40.6%). Twelve contained\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations. Nine (75%) shared identical\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations with concurrent HGSCs, four at high (\u2265 5%) and five at low (&lt; 5%) allele frequency. All control epithelia were\n                    <jats:italic>TP53<\/jats:italic>\n                    mutation\u2010negative. This study, for the first time, indicates lineage identity between ESPs in the distal tube and some metastatic HGSCs via a shared site\u2010specific\n                    <jats:italic>TP53<\/jats:italic>\n                    mutation. It supports a novel serous carcinogenic sequence in which an ESP could eventually culminate in a metastatic serous cancer via \u2018precursor escape\u2019 and would explain the apparent sudden onset of cancers without co\u2010existing STICs. This paradigm for serous cancer development underscores the likelihood that multiple precursor types in the Fallopian tube contribute to serous cancer development with implications for the evolution, pathologic classification, and prevention of this lethal malignancy. Copyright \u00a9 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.5145","type":"journal-article","created":{"date-parts":[[2018,7,25]],"date-time":"2018-07-25T04:35:24Z","timestamp":1532493324000},"page":"344-351","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Evidence for lineage continuity between early serous proliferations (ESPs) in the Fallopian tube and disseminated high\u2010grade serous carcinomas"],"prefix":"10.1002","volume":"246","author":[{"given":"Thing Rinda","family":"Soong","sequence":"first","affiliation":[{"name":"Division of Women's and Perinatal Pathology, Department of Pathology Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke E","family":"Howitt","sequence":"additional","affiliation":[{"name":"Department of Pathology Stanford University Medical Center  Palo Alto California 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G","family":"Muto","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross S","family":"Berkowitz","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa R","family":"Nucci","sequence":"additional","affiliation":[{"name":"Division of Women's and Perinatal Pathology, Department of Pathology Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wa","family":"Xian","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine University of Texas Health Sciences Center  Houston Texas 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