| Title: |
CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma : an ovarian tumor tissue analysis consortium study |
| Authors: |
Kang, Eun-Young; Weir, Ashley; Meagher, Nicola S; Farrington, Kyo; Nelson, Gregg S; Ghatage, Prafull; Lee, Cheng-Han; Riggan, Marjorie J; Bolithon, Adelyn; Popovic, Gordana; Leung, Betty; Tang, Katrina; Lambie, Neil; Millstein, Joshua; Alsop, Jennifer; Anglesio, Michael S; Ataseven, Beyhan; Barlow, Ellen; Beckmann, Matthias W; Berger, Jessica; Bisinotto, Christiani; Bösmüller, Hans; Boros, Jessica; Brand, Alison H; Brooks-Wilson, Angela; Brucker, Sara Y; Carney, Michael E; Casablanca, Yovanni; Cazorla-Jiménez, Alicia; Cohen, Paul A; Conrads, Thomas P; Cook, Linda S; Coulson, Penny; Courtney-Brooks, Madeleine; Cramer, Daniel W; Crowe, Philip; Cunningham, Julie M; Cybulski, Cezary; Darcy, Kathleen M; El-Bahrawy, Mona A; Elishaev, Esther; Erber, Ramona; Farrell, Rhonda; Fereday, Sian; Fischer, Anna; García, María J; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Gilks, C Blake; missing , missing; Grube, Marcel; Harnett, Paul R; Harrington, Shariska Petersen; Harter, Philipp; Hartmann, Arndt; Hecht, Jonathan L; Heikaus, Sebastian; Hein, Alexander; Heitz, Florian; Hendley, Joy; Hernandez, Brenda Y; Polo, Susanna Hernando; Heublein, Sabine; Hirasawa, Akira; Høgdall, Estrid; Høgdall, Claus K; Horlings, Hugo M; Huntsman, David G; Huzarski, Tomasz; Jewell, Andrea; Jimenez-Linan, Mercedes; Jones, Michael E; Kaufmann, Scott H; Kennedy, Catherine J; Khabele, Dineo; Kommoss, Felix K F; Kruitwagen, Roy F P M; Lambrechts, Diether; Le, Nhu D; Lener, Marcin; Lester, Jenny; Leung, Yee; Linder, Anna; Loverix, Liselore; Lubiński, Jan; Madan, Rashna; Maxwell, G Larry; Modugno, Francesmary; Neuhausen, Susan L; Olawaiye, Alexander; Olbrecht, Siel; Orsulic, Sandra; Palacios, José; Pearce, Celeste Leigh; Pike, Malcolm C; Quinn, Carmel M; Mohan, Ganendra Raj; Rodríguez-Antona, Cristina; Ruebner, Matthias; Ryan, Andy; Salfinger, Stuart G; Sasamoto, Naoko; Schildkraut, Joellen M; Schoemaker, Minouk J; Shah, Mitul; Sharma, Raghwa; Shvetsov, Yurii B; Singh, Naveena; Sonke, Gabe S; Steele, Linda; Stewart, Colin J R; Sundfeldt, Karin; Swerdlow, Anthony J; Talhouk, Aline; Tan, Adeline; Taylor, Sarah E; Terry, Kathryn L; Tołoczko, Aleksandra; Traficante, Nadia; Van de Vijver, Koen; van der Aa, Maaike A; Van Gorp, Toon; Van Nieuwenhuysen, Els; van-Wagensveld, Lilian; Vergote, Ignace; Vierkant, Robert A; Wang, Chen; Wilkens, Lynne R; Winham, Stacey J; Wu, Anna H; Benitez, Javier; Berchuck, Andrew; Candido Dos Reis, Francisco J; DeFazio, Anna; Fasching, Peter A; Goode, Ellen L; Goodman, Marc T; Gronwald, Jacek; Karlan, Beth Y; Kommoss, Stefan; Menon, Usha; Sinn, Hans-Peter; Staebler, Annette; Brenton, James D; Bowtell, David D; Pharoah, Paul D P; Ramus, Susan J; Köbel, Martin; Grp, AOCS |
| Source: |
CANCER ; ISSN: 0008-543X ; ISSN: 1097-0142 |
| Publication Year: |
2023 |
| Collection: |
Ghent University Academic Bibliography |
| Subject Terms: |
Medicine and Health Sciences; prognosis; ovarian cancer; high-grade serous carcinoma; cyclin E1 expression; CCNE1 amplification |
| Description: |
Background: 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. Methods: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. Results: 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. Conclusion: 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://biblio.ugent.be/publication/01HSZNG1BZ0M23MQHJE477M8BS; https://doi.org/10.1002/cncr.34582; https://biblio.ugent.be/publication/01HSZNG1BZ0M23MQHJE477M8BS/file/01HSZNGHFE3E42459E163S54N2 |
| DOI: |
10.1002/cncr.34582 |
| Availability: |
https://biblio.ugent.be/publication/01HSZNG1BZ0M23MQHJE477M8BS; https://hdl.handle.net/1854/LU-01HSZNG1BZ0M23MQHJE477M8BS; https://doi.org/10.1002/cncr.34582; https://biblio.ugent.be/publication/01HSZNG1BZ0M23MQHJE477M8BS/file/01HSZNGHFE3E42459E163S54N2 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.52C8508E |
| Database: |
BASE |