CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.
- 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:
- E-Y Kang, A Weir, NS Meagher, K Farrington, GS Nelson, P Ghatage, C-H Lee, MJ Riggan, A Bolithon, G Popovic, B Leung, K Tang, N Lambie, J Millstein, J Alsop, MS Anglesio, B Ataseven, E Barlow, MW Beckmann, J Berger, C Bisinotto, H Bösmüller, J Boros, AH Brand, A Brooks-Wilson, SY Brucker, ME Carney, Y Casablanca, A Cazorla-Jiménez, PA Cohen, TP Conrads, LS Cook, P Coulson, M Courtney-Brooks, DW Cramer, P Crowe, JM Cunningham, C Cybulski, KM Darcy, MA El-Bahrawy, E Elishaev, R Erber, R Farrell, S Fereday, A Fischer, MJ García, SA Gayther, A Gentry-Maharaj, CB Gilks, AOCS Group, M Grube, PR Harnett, SP Harrington, P Harter, A Hartmann, JL Hecht, S Heikaus, A Hein, F Heitz, J Hendley, BY Hernandez, SH Polo, S Heublein, A Hirasawa, E Høgdall, CK Høgdall, HM Horlings, DG Huntsman, T Huzarski, A Jewell, M Jimenez-Linan, ME Jones, SH Kaufmann, CJ Kennedy, D Khabele, FKF Kommoss, RFPM Kruitwagen, D Lambrechts, ND Le, M Lener, J Lester, Y Leung, A Linder, L Loverix, J Lubiński, R Madan, GL Maxwell, F Modugno, SL Neuhausen, A Olawaiye, S Olbrecht, S Orsulic, J Palacios, CL Pearce, MC Pike, CM Quinn, GR Mohan, C Rodríguez-Antona, M Ruebner, A Ryan, SG Salfinger, N Sasamoto, JM Schildkraut, MJ Schoemaker, M Shah, R Sharma, YB Shvetsov, N Singh, GS Sonke, L Steele, CJR Stewart, K Sundfeldt, AJ Swerdlow, A Talhouk, A Tan, SE Taylor, KL Terry, A Tołoczko, N Traficante, KK Van de Vijver, MA van der Aa, T Van Gorp, E Van Nieuwenhuysen, L van-Wagensveld, I Vergote, RA Vierkant, C Wang, LR Wilkens, SJ Winham, AH Wu, J Benitez, A Berchuck, FJ Candido Dos Reis, A DeFazio, PA Fasching, EL Goode, MT Goodman, J Gronwald, BY Karlan, S Kommoss, U Menon, H-P Sinn, A Staebler, JD Brenton, DD Bowtell, PDP Pharoah, SJ Ramus, M Köbel
- Journal:
- Cancer
- Citation info:
- 129(5):697-713
- Publication date:
- 1st Mar 2023
- Full text
- DOI