{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:08:07Z","timestamp":1791616087997,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,7,8]],"date-time":"2011-07-08T00:00:00Z","timestamp":1310083200000},"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":[[2011,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The discovery of occult invasive and intra\u2010epithelial tubal carcinomas in <jats:italic>BRCA1<\/jats:italic> mutation carriers undergoing prophylactic surgery has implicated the fallopian tube epithelium as the source of serous cancer. However, little is known of the early molecular events of serous oncogenesis, or why cancers in <jats:italic>BRCA1<\/jats:italic> mutation carriers are found preferentially in tissues which are responsive to reproductive hormones. We hypothesize that molecular alterations present in morphologically normal tubal epithelium from <jats:italic>BRCA1<\/jats:italic> heterozygotes reflect the earliest events in serous carcinogenesis and may be markers of increased cancer risk as well as targets for risk reduction. Genetic profiling of microdissected tubal epithelium from histologically normal <jats:italic>BRCA1<\/jats:italic> mutation carriers and controls was performed. We sought to define a signature which differentiated <jats:italic>BRCA1<\/jats:italic> mutant tubal epithelium from women with low risk of developing ovarian cancer. Molecular differences between the follicular and luteal phases were prominent and, by using filtering techniques and a two\u2010way ANOVA without a False Discovery Rate correction, we identified 440 probe sets with a more than two\u2010fold change in gene expression related to <jats:italic>BRCA1<\/jats:italic> mutation status. Using gene ontology and known associations to cancer pathways, we selected five genes for further analysis by qPCR and immunohistochemistry, and were able to demonstrate statistically significant differentiation of <jats:italic>BRCA1<\/jats:italic> and control cases in an independent set of cases. The altered expression profiles in histologically normal tubal epithelium from <jats:italic>BRCA1<\/jats:italic> heterozygotes suggest that these cells may respond differently to microenvironmental stresses.   Copyright \u00a9 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2927","type":"journal-article","created":{"date-parts":[[2011,4,26]],"date-time":"2011-04-26T07:31:32Z","timestamp":1303803092000},"page":"106-117","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Identification of abrogated pathways in fallopian tube epithelium from <i>BRCA1<\/i> mutation carriers"],"prefix":"10.1002","volume":"225","author":[{"given":"Sophia 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