CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

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

Journal

Book Volume: 129

Pages Range: 697-713

Journal Issue: 5

DOI: 10.1002/cncr.34582

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.

Authors with CRIS profile

Involved external institutions

Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Cedars-Sinai Medical Center United States (USA) (US) University College London (UCL) United Kingdom (GB) University of British Columbia Canada (CA) University of Sydney (USYD) Australia (AU) University of Kansas Medical Center United States (USA) (US) University of São Paulo / Universidade de São Paulo (USP) Brazil (BR) University of Alberta Canada (CA) Duke University United States (USA) (US) University of New South Wales (UNSW) Australia (AU) Prince of Wales Hospital (POWH) Australia (AU) Canterbury Health Laboratories New Zealand (NZ) University of Calgary Canada (CA) Keck School of Medicine of USC United States (USA) (US) University of Cambridge United Kingdom (GB) Kliniken Essen-Mitte Germany (DE) Royal Hospital for Women Australia (AU) University of Pittsburgh United States (USA) (US) Universitätsklinikum Tübingen Germany (DE) Westmead Hospital Australia (AU) British Columbia Cancer Agency Canada (CA) Uniformed Services University United States (USA) (US) University of Colorado Anschutz Medical Campus United States (USA) (US) University of Hawaii (U.H.) United States (USA) (US) Fundación Jiménez Díaz Spain (ES) St John of God Health Care Australia (AU) Inova Health System United States (USA) (US) The Institute of Cancer Research (ICR) United Kingdom (GB) Brigham and Women's Hospital (BWH) United States (USA) (US) Mayo Clinic United States (USA) (US) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Hammersmith Hospital United Kingdom (GB) Okayama University / 岡山大学 Japan (JP) University of Copenhagen Denmark (DK) Netherlands Cancer Institute (NKI) Netherlands (NL) Peter MacCallum Cancer Centre Australia (AU) Veterans Affairs Healthcare System Boston and Harvard Medical School United States (USA) (US) Hospital Universitario Fundación Alcorcón (HUFA) Spain (ES) Universitätsklinikum Heidelberg Germany (DE) University of California Los Angeles (UCLA) United States (USA) (US) University of Gothenburg / Göteborgs universitet Sweden (SE) Addenbrooke's Hospital United Kingdom (GB) Washington University United States (USA) (US) Maastricht University Netherlands (NL) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) Emory University United States (USA) (US) Barts Health NHS Trust United Kingdom (GB) Antoni van Leeuwenhoek Netherlands (NL) City of Hope Medical Center United States (USA) (US) Universidad de Alcalá (UAH) Spain (ES) University of Michigan–Ann Arbor United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) Netherlands Comprehensive Cancer Organisation / Integraal Kankercentrum Nederland (IKNL) Netherlands (NL) University Hospital Ghent Belgium (BE) Ciber de Enfermedades Raras (CIBERER) Spain (ES)

How to cite

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://dx.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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