Kang EY, Weir A, Meagher NS, Farrington K, Nelson GS, Ghatage P, Lee CH, Riggan MJ, Bolithon A, Popovic G, Leung B, Tang K, Lambie N, Millstein J, Alsop J, Anglesio MS, Ataseven B, Barlow E, Beckmann M, Berger J, Bisinotto C, Bösmüller H, Boros J, Brand AH, Brooks-Wilson A, Brucker SY, Carney ME, Casablanca Y, Cazorla-Jiménez A, Cohen PA, Conrads TP, Cook LS, Coulson P, Courtney-Brooks M, Cramer DW, Crowe P, Cunningham JM, Cybulski C, Darcy KM, El-Bahrawy MA, Elishaev E, Erber R, Farrell R, Fereday S, Fischer A, García MJ, Gayther SA, Gentry-Maharaj A, Gilks CB, Grube M, Harnett PR, Harrington SP, Harter P, Hartmann A, Hecht JL, Heikaus S, Hein A, Heitz F, Hendley J, Hernandez BY, Polo SH, Heublein S, Hirasawa A, Høgdall E, Høgdall CK, Horlings HM, Huntsman DG, Huzarski T, Jewell A, Jimenez-Linan M, Jones ME, Kaufmann SH, Kennedy CJ, Khabele D, Kommoss FK, Kruitwagen RF, Lambrechts D, Le ND, Lener M, Lester J, Leung Y, Linder A, Loverix L, Lubiński J, Madan R, Maxwell GL, Modugno F, Neuhausen SL, Olawaiye A, Olbrecht S, Orsulic S, Palacios J, Pearce CL, Pike MC, Quinn CM, Mohan GR, Rodríguez-Antona C, Rübner M, Ryan A, Salfinger SG, Sasamoto N, Schildkraut JM, Schoemaker MJ, Shah M, Sharma R, Shvetsov YB, Singh N, Sonke GS, Steele L, Stewart CJ, Sundfeldt K, Swerdlow AJ, Talhouk A, Tan A, Taylor SE, Terry KL, Tołoczko A, Traficante N, Van de Vijver KK, van der Aa MA, Van Gorp T, Van Nieuwenhuysen E, van-Wagensveld L, Vergote I, Vierkant RA, Wang C, Wilkens LR, Winham SJ, Wu AH, Benitez J, Berchuck A, Candido dos Reis FJ, DeFazio A, Fasching P, Goode EL, Goodman MT, Gronwald J, Karlan BY, Kommoss S, Menon U, Sinn HP, Staebler A, Brenton JD, Bowtell DD, Pharoah PD, Ramus SJ, Köbel M (2023)
Publication Type: Journal article
Publication year: 2023
Book Volume: 129
Pages Range: 697-713
Journal Issue: 5
DOI: 10.1002/cncr.34582
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.
APA:
Kang, E.Y., Weir, A., Meagher, N.S., Farrington, K., Nelson, G.S., Ghatage, P.,... Köbel, M. (2023). CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study. Cancer, 129(5), 697-713. https://doi.org/10.1002/cncr.34582
MLA:
Kang, Eun Young, et al. "CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study." Cancer 129.5 (2023): 697-713.
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