{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:28:01Z","timestamp":1791325681897,"version":"4.3.1"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,11,20]],"date-time":"2006-11-20T00:00:00Z","timestamp":1163980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2007,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The tubal fimbria is a common site of origin for early (tubal intraepithelial carcinoma or TIC) serous carcinomas in women with familial\n                    <jats:italic>BRCA1<\/jats:italic>\n                    or\n                    <jats:italic>2<\/jats:italic>\n                    mutations (BRCA+). Somatic\n                    <jats:italic>p53<\/jats:italic>\n                    tumour suppressor gene mutations in these tumours suggest a pathogenesis involving DNA damage,\n                    <jats:italic>p53<\/jats:italic>\n                    mutation, and progressive loss of cell cycle control. We recently identified foci of strong p53 immunostaining\u2014termed \u2018p53 signatures\u2019\u2014in benign tubal mucosa from BRCA+ women. To examine the relationship between p53 signatures and TIC, we compared location (fimbria vs ampulla), cell type (ciliated vs secretory), evidence of DNA damage, and\n                    <jats:italic>p53<\/jats:italic>\n                    mutation status between the two entities. p53 signatures were equally common in non\u2010neoplastic tubes from BRCA+ women and controls, but more frequently present (53%) and multifocal (67%) in fallopian tubes also containing TIC. Like prior studies of TIC, p53 signatures predominated in the fimbriae (80\u2013100%) and targeted secretory cells (HMFG2 + \/p73\u2212), with evidence of DNA damage by co\u2010localization of \u03b3\u2010H2AX. Laser\u2010capture microdissected and polymerase chain reaction\u2010amplified DNA revealed reproducible\n                    <jats:italic>p53<\/jats:italic>\n                    mutations in eight of 14 fully\u2010analysed p53 signatures and all of the 12 TICs; TICs and their associated ovarian carcinomas shared identical mutations. In one case, a contiguous p53 signature and TIC shared the same mutation. Morphological intermediates between the two, with\n                    <jats:italic>p53<\/jats:italic>\n                    mutations and moderate proliferative activity, were also seen. This is the first report of an early and distinct alteration in non\u2010neoplastic upper genital tract mucosa that fulfils many requirements for a precursor to pelvic serous cancer. The p53 signature and its malignant counterpart (TIC) underline the significance of the fimbria, both as a candidate site for serous carcinogenesis and as a target for future research on the early detection and prevention of this disease. Copyright \u00a9 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.2091","type":"journal-article","created":{"date-parts":[[2006,11,20]],"date-time":"2006-11-20T10:55:35Z","timestamp":1164020135000},"page":"26-35","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":781,"title":["A candidate precursor to serous carcinoma that originates in the distal fallopian tube"],"prefix":"10.1002","volume":"211","author":[{"given":"Y","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Miron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Drapkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MR","family":"Nucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Medeiros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Saleemuddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Garber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Birch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Mou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RW","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DW","family":"Cramer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FD","family":"McKeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CP","family":"Crum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,11,20]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2005.06.052"},{"key":"e_1_2_6_3_2","volume-title":"WHO world cancer report","author":"Stewart BW","year":"2003"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19890701)64:1<110::AID-CNCR2820640120>3.0.CO;2-5"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63708-X"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041842"},{"key":"e_1_2_6_7_2","first-page":"467","article-title":"Current issues in the pathology of ovarian cancer","volume":"50","author":"Rabban JT","year":"2005","journal-title":"J Reprod Med"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000146025.91953.8d"},{"key":"e_1_2_6_9_2","first-page":"20","article-title":"Prevention of ovarian cancer: intraepithelial neoplasia","volume":"9","author":"Brewer MA","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1995.tb01528.x"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1000"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19940401)73:7<1859::AID-CNCR2820730714>3.0.CO;2-L"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20000715)89:2<383::AID-CNCR25>3.0.CO;2-T"},{"key":"e_1_2_6_14_2","first-page":"793","volume-title":"Diagnostic Gynecologic and Obstetric Pathology","author":"Drapkin RL","year":"2006"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200110000-00009"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000180854.28831.77"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000187892.78392.3f"},{"key":"e_1_2_6_18_2","article-title":"Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship","author":"Kindelberger D","year":"2006","journal-title":"Am J Surg Pathol"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03485"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2005.04.003"},{"key":"e_1_2_6_21_2","first-page":"107","article-title":"Aberrant crypt foci","volume":"26","author":"Alrawi SJ","year":"2006","journal-title":"Anticancer Res"},{"key":"e_1_2_6_22_2","first-page":"1791","article-title":"Benign clonal keratinocyte patches with p53 mutations show no genetic link to synchronous squamous cell precancer or cancer in human skin","volume":"150","author":"Ren ZP","year":"1997","journal-title":"Am J Pathol"},{"key":"e_1_2_6_23_2","first-page":"867","article-title":"Immunobiochemical and molecular biologic characterization of the cell proliferation\u2010associated nuclear antigen that is defined by monoclonal antibody Ki\u201067","volume":"138","author":"Gerdes J","year":"1991","journal-title":"Am J Pathol"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/13.11.3114"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.52.5.355"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.05.008"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.024"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.5.2.2530"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03482"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65461-2"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00496577"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.877335"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2004.01.043"},{"key":"e_1_2_6_34_2","first-page":"4855","article-title":"Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis","volume":"54","author":"Greenblatt MS","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_6_35_2","first-page":"1699","article-title":"Aberrant expression of the p53 oncoprotein is a common feature of a wide spectrum of human malignancies","volume":"6","author":"Bartek J","year":"1991","journal-title":"Oncogene"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2004.11.020"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.03.183"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod65.5.1417"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.105.042622"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.2091","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.2091","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T11:00:26Z","timestamp":1761044426000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.2091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,11,20]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,1]]}},"alternative-id":["10.1002\/path.2091"],"URL":"https:\/\/doi.org\/10.1002\/path.2091","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,11,20]]},"assertion":[{"value":"2006-08-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-09-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-11-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}