{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T06:23:31Z","timestamp":1769063011293,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2010,7,27]],"date-time":"2010-07-27T00:00:00Z","timestamp":1280188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2010,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p><jats:italic>BRCA1<\/jats:italic> or <jats:italic>BRCA2<\/jats:italic> (<jats:italic>BRCA1\/2<\/jats:italic>)\u2010mutated ovarian carcinomas may originate in the fallopian tube. The authors of this report investigated alterations in <jats:italic>BRCA1\/2<\/jats:italic> tubal epithelium to define the molecular pathogenesis of these carcinomas.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>Tubal epithelium was evaluated from 31 <jats:italic>BRCA1\/2<\/jats:italic> mutation carriers with gynecologic carcinomas (<jats:italic>BRCA<\/jats:italic> CA), 89 mutation carriers who underwent risk\u2010reducing salpingo\u2010oophorectomy (RRSO), and 87 controls. Ki\u201067 expression and p53 foci (\u226510 of 12 consecutive staining cells) were scored by 2 investigators who were blinded to patient designations. Expression levels of p27 and p21 were evaluated within p53 foci. Loss of heterozygosity at the <jats:italic>BRCA1\/2<\/jats:italic> mutation site was evaluated in microdissected p53 foci and tubal neoplasms.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>Background tubal proliferation as measured by Ki\u201067 staining was increased in the <jats:italic>BRCA1<\/jats:italic> RRSO group (<jats:italic>P<\/jats:italic> = .005) compared with the control group. Women who had <jats:italic>BRCA1\/2<\/jats:italic> mutations had more p53 foci identified per tubal segment than women in the control group (<jats:italic>P<\/jats:italic> = .02). Levels of p27 were decreased in 12 of 28 p53 foci from women with <jats:italic>BRCA1<\/jats:italic> mutations and in 0 of 16 p53 foci from controls (<jats:italic>P<\/jats:italic> = .002). There was no loss of the wild type <jats:italic>BRCA1\/2<\/jats:italic> allele in 5 tested p53 foci. Tubal neoplasia lost the wild type allele in 6 of 6 foci (<jats:italic>P<\/jats:italic> = .002).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>The current results suggested a model of tubal carcinogenesis in women with <jats:italic>BRCA1\/2<\/jats:italic> mutations. Increased proliferation occurred globally in at\u2010risk tubal epithelium. A mutation in the tumor protein p53 gene <jats:italic>TP53<\/jats:italic> with clonal proliferation and loss of p27 occurred before neoplastic proliferation. Loss of the wild type <jats:italic>BRCA1\/2<\/jats:italic> allele occurred with neoplastic proliferation and before invasion. Cancer 2010. \u00a9 2010 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.25439","type":"journal-article","created":{"date-parts":[[2010,7,27]],"date-time":"2010-07-27T20:03:08Z","timestamp":1280260988000},"page":"5261-5271","source":"Crossref","is-referenced-by-count":95,"title":["The molecular pathogenesis of hereditary ovarian carcinoma"],"prefix":"10.1002","volume":"116","author":[{"given":"Barbara M.","family":"Norquist","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rochelle L.","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly H.","family":"Allison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris H.","family":"Jokinen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren 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