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-Jimenez, 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; Garcia, Maria J.; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Gilks, C. Blake; 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.; Hernando Polo, Susanna; Heublein, Sabine; Hirasawa, Akira; Hogdall, Estrid; Hogdall, 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; Lubinski, Jan; Madan, Rashna; Maxwell, G. Larry; Modugno, Francesmary; Neuhausen, Susan L.; Olawaiye, Alexander; Olbrecht, Siel; Orsulic, Sandra; Palacios, Jose; Pearce, Celeste Leigh; Pike, Malcolm C.; Quinn, Carmel M.; Mohan, Ganendra Raj; Rodriguez-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.; Toloczko, Aleksandra; Traficante, Nadia; Vijver, Koen K. van de; Aa, Maaike A. van der; Gorp, Toon van; Nieuwenhuysen, Els van; Wagensveld, Lilian van; 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. und Köbel, Martin
(2022):
CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.
In: Cancer, Bd. 129, Nr. 5: S. 697-713
Volltext auf 'Open Access LMU' nicht verfügbar.
Abstract
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.
- Dokument bearbeiten
