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oai:repisalud.isciii.es:20.500.12105/265292025-12-18T12:51:45Zcom_20.500.12105_2273com_20.500.12105_2202col_20.500.12105_19571

00925njm 22002777a 4500 dc Kang, Eun-Young author Weir, Ashley author Meagher, Nicola S author Farrington, Kyo author Nelson, Gregg S author Ghatage, Prafull author Lee, Cheng-Han author Riggan, Marjorie J author Bolithon, Adelyn author Popovic, Gordana author Leung, Betty author Tang, Katrina author Lambie, Neil author Millstein, Joshua author Alsop, Jennifer author Anglesio, Michael S author Ataseven, Beyhan author Barlow, Ellen author Beckmann, Matthias W author Berger, Jessica author Bisinotto, Christiani author Bösmüller, Hans author Boros, Jessica author Brand, Alison H author Brooks-Wilson, Angela author Brucker, Sara Y author Carney, Michael E author Casablanca, Yovanni author Cazorla-Jiménez, Alicia author Cohen, Paul A author Conrads, Thomas P author Cook, Linda S author Coulson, Penny author Courtney-Brooks, Madeleine author Cramer, Daniel W author Crowe, Philip author Cunningham, Julie M author Cybulski, Cezary author Darcy, Kathleen M author El-Bahrawy, Mona A author Elishaev, Esther author Erber, Ramona author Farrell, Rhonda author Fereday, Sian author Fischer, Anna author García, María J author Gayther, Simon A author Gentry-Maharaj, Aleksandra author Gilks, C Blake author Grube, Marcel author Harnett, Paul R author Harrington, Shariska Petersen author Harter, Philipp author Hartmann, Arndt author Hecht, Jonathan L author Heikaus, Sebastian author Hein, Alexander author Heitz, Florian author Hendley, Joy author Hernandez, Brenda Y author Polo, Susanna Hernando author Heublein, Sabine author Hirasawa, Akira author Høgdall, Estrid author Høgdall, Claus K author Horlings, Hugo M author Huntsman, David G author Huzarski, Tomasz author Jewell, Andrea author Jimenez-Linan, Mercedes author Jones, Michael E author Kaufmann, Scott H author Kennedy, Catherine J author Khabele, Dineo author Kommoss, Felix K F author Kruitwagen, Roy F P M author Lambrechts, Diether author Le, Nhu D author Lener, Marcin author Lester, Jenny author Leung, Yee author Linder, Anna author Loverix, Liselore author Lubiński, Jan author Madan, Rashna author Maxwell, G Larry author Modugno, Francesmary author Neuhausen, Susan L author Olawaiye, Alexander author Olbrecht, Siel author Orsulic, Sandra author Palacios, José author Pearce, Celeste Leigh author Pike, Malcolm C author Quinn, Carmel M author Mohan, Ganendra Raj author Rodríguez-Antona, Cristina author Ruebner, Matthias author Ryan, Andy author Salfinger, Stuart G author Sasamoto, Naoko author Schildkraut, Joellen M author Schoemaker, Minouk J author Shah, Mitul author Sharma, Raghwa author Shvetsov, Yurii B author Singh, Naveena author Sonke, Gabe S author Steele, Linda author Stewart, Colin J R author Sundfeldt, Karin author Swerdlow, Anthony J author Talhouk, Aline author Tan, Adeline author Taylor, Sarah E author Terry, Kathryn L author Tołoczko, Aleksandra author Traficante, Nadia author Van de Vijver, Koen K author van der Aa, Maaike A author Van Gorp, Toon author Van Nieuwenhuysen, Els author van-Wagensveld, Lilian author Vergote, Ignace author Vierkant, Robert A author Wang, Chen author Wilkens, Lynne R author Winham, Stacey J author Wu, Anna H author Benitez, Javier author Berchuck, Andrew author Candido Dos Reis, Francisco J author DeFazio, Anna author Fasching, Peter A author Goode, Ellen L author Goodman, Marc T author Gronwald, Jacek author Karlan, Beth Y author Kommoss, Stefan author Menon, Usha author Sinn, Hans-Peter author Staebler, Annette author Brenton, James D author Bowtell, David D author Pharoah, Paul D P author Ramus, Susan J author Köbel, Martin author 2023-03-01 Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. High-level amplification (>8 copies by chromogenic in situ 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 high-level 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], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC. Cancer . 2023 Mar 1;129(5):697-713. Cancer 36572991 https://hdl.handle.net/20.500.12105/26529 CCNE1 amplification cyclin E1 expression high-grade serous carcinoma ovarian cancer prognosis CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.