| 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; AOCS Group; 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 KF; Kruitwagen, Roy FPM; 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 JR; Sundfeldt, Karin; Swerdlow, Anthony J; Talhouk, Aline; Tan, Adeline; Taylor, Sarah E; Terry, Kathryn L; Tołoczko, Aleksandra; Traficante, Nadia; Van de Vijver, Koen K; 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 DP; Ramus, Susan J; Köbel, Martin |
| Source: |
Cancer , 129 (5) pp. 697-713. (2022) |
| Publisher Information: |
Wiley |
| Publication Year: |
2022 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
CCNE1 amplification; cyclin E1 expression; high-grade serous carcinoma; ovarian cancer; prognosis |
| 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: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10164476/1/CCNE1%20and%20survival%20of%20patients%20with%20tubo%20ovarian%20high%20grade%20serous%20carcinoma.pdf; https://discovery.ucl.ac.uk/id/eprint/10164476/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10164476/1/CCNE1%20and%20survival%20of%20patients%20with%20tubo%20ovarian%20high%20grade%20serous%20carcinoma.pdf; https://discovery.ucl.ac.uk/id/eprint/10164476/ |
| Rights: |
open |
| Accession Number: |
edsbas.34889DD7 |
| Database: |
BASE |