{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:30:27Z","timestamp":1792456227376,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,12,26]],"date-time":"2022-12-26T00:00:00Z","timestamp":1672012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA172404"],"award-info":[{"award-number":["R01CA172404"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019089","name":"Alberta Precision Laboratories","doi-asserted-by":"publisher","award":["RS17\u2010601, RS10\u2010526"],"award-info":[{"award-number":["RS17\u2010601, RS10\u2010526"]}],"id":[{"id":"10.13039\/100019089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2023,3]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo\u2010ovarian high\u2010grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1<\/jats:italic> amplification and CCNE1 overexpression with survival, but to date no large\u2010scale, histotype\u2010specific validation has been performed. The hypothesis was that high\u2010level amplification of CCNE1<\/jats:italic> and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC.<\/jats:p><\/jats:sec>Methods<\/jats:title>Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated.<\/jats:p><\/jats:sec>Results<\/jats:title>High\u2010level amplification (>8 copies by chromogenic in situ<\/jats:italic> hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1<\/jats:italic> high\u2010level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR],\u00a01.26; 95% CI, 1.08\u20101.47, p<\/jats:italic>\u00a0=\u00a0.034, and HR,\u00a01.18; 95% CI, 1.05\u20101.32, p<\/jats:italic>\u00a0=\u00a0.015, respectively). This was also true for cases with combined high\u2010level amplification\/overexpression (HR,\u00a01.26; 95% CI, 1.09\u20101.47, p<\/jats:italic>\u00a0=\u00a0.033). CCNE1<\/jats:italic> mRNA expression was not associated with overall survival (HR,\u00a01.00 per 1\u2010SD increase; 95% CI, 0.94\u20101.06; p<\/jats:italic>\u00a0=\u00a0.58). CCNE1<\/jats:italic> high\u2010level amplification is mutually exclusive with the presence of germline BRCA1\/2<\/jats:italic> pathogenic variants and shows an inverse association to RB1 loss.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>This study provides large\u2010scale validation that CCNE1<\/jats:italic> high\u2010level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.34582","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T00:41:47Z","timestamp":1672101707000},"page":"697-713","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["CCNE1 and survival of patients with tubo\u2010ovarian high\u2010grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study"],"prefix":"10.1002","volume":"129","author":[{"given":"Eun\u2010Young","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Calgary Foothills Medical Center Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Weir","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine UNSW Medicine and Health University of NSW Sydney Sydney New South Wales Australia"},{"name":"Adult Cancer Program Lowy Cancer Research Centre University of NSW Sydney Sydney New South Wales Australia"},{"name":"The Walter and Eliza Hall Institute of Medical Research Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9134-2118","authenticated-orcid":false,"given":"Nicola S.","family":"Meagher","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine UNSW Medicine and Health 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