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, MW; Berger, J; Bisinotto, C; Bosmuller, H; Boros, J; Brand, AH; Brooks-Wilson, A; Brucker, SY; Carney, ME; Casablanca, Y; Cazorla-Jimenez, 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; Garcia, MJ; Gayther, SA; Gentry-Maharaj, A; Gilks, CB; AOCS Group; Grube, M; Harnett, PR; Harrington, SP; Harter, P; Hartmann, A; Hecht, JL; Heikaus, S; Hein, A; Heitz, F; Hendley, J; Hernandez, BY; Hernando Polo, S; Heublein, S; Hirasawa, A; Hogdall, E; Hogdall, CK; Horlings, HM; Huntsman, DG; Huzarski, T; Jewell, A; Jimenez-Linan, M; Jones, ME; Kaufmann, SH; Kennedy, CJ; Khabele, D; Kommoss, FKF; Kruitwagen, RFPM; Lambrechts, D; Le, ND; Lener, M; Lester, J; Leung, Y; Linder, A; Loverix, L; Lubinski, 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; Rodriguez-Antona, C; Ruebner, M; Ryan, A; Salfinger, SG; Sasamoto, N; Schildkraut, JM; Schoemaker, MJ; Shah, M; Sharma, R; Shvetsov, YB; Singh, N; Sonke, GS; Steele, L; Stewart, CJR; Sundfeldt, K; Swerdlow, AJ; Talhouk, A; Tan, A; Taylor, SE; Terry, KL; Toloczko, 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, PA; Goode, EL; Goodman, MT; Gronwald, J; Karlan, BY; Kommoss, S; Menon, U; Sinn, HP; Staebler, A; Brenton, JD; Bowtell, DD; Pharoah, PDP; Ramus, SJ; Kobel, M

Author(s): 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, MW; Berger, J; Bisinotto, C; Bosmuller, H; Boros, J; Brand, AH; Brooks-Wilson, A; Brucker, SY; Carney, ME; Casablanca, Y; Cazorla-Jimenez, 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; Garcia, MJ; Gayther, SA; Gentry-Maharaj, A; Gilks, CB; AOCS Group; Grube, M; Harnett, PR; Harrington, SP; Harter, P; Hartmann, A; Hecht, JL; Heikaus, S; Hein, A; Heitz, F; Hendley, J; Hernandez, BY; Hernando Polo, S; Heublein, S; Hirasawa, A; Hogdall, E; Hogdall, CK; Horlings, HM; Huntsman, DG; Huzarski, T; Jewell, A; Jimenez-Linan, M; Jones, ME; Kaufmann, SH; Kennedy, CJ; Khabele, D; Kommoss, FKF; Kruitwagen, RFPM; Lambrechts, D; Le, ND; Lener, M; Lester, J; Leung, Y; Linder, A; Loverix, L; Lubinski, 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; Rodriguez-Antona, C; Ruebner, M; Ryan, A; Salfinger, SG; Sasamoto, N; Schildkraut, JM; Schoemaker, MJ; Shah, M; Sharma, R; Shvetsov, YB; Singh, N; Sonke, GS; Steele, L; Stewart, CJR; Sundfeldt, K; Swerdlow, AJ; Talhouk, A; Tan, A; Taylor, SE; Terry, KL; Toloczko, 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, PA; Goode, EL; Goodman, MT; Gronwald, J; Karlan, BY; Kommoss, S; Menon, U; Sinn, HP; Staebler, A; Brenton, JD; Bowtell, DD; Pharoah, PDP; Ramus, SJ; Kobel, M;
Details: Publication Year 2023-03-01,Volume 129,Issue #5,Page 697-713
Journal Title: Cancer
Publication Type: Research article
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.
Publisher: Wiley
Keywords: Female; Humans; *Ovarian Neoplasms/pathology; Transcription Factors/genetics; *Carcinoma; RNA, Messenger; *Cystadenocarcinoma, Serous/genetics; Oncogene Proteins/genetics/therapeutic use; Cyclin E/genetics; CCNE1 amplification; cyclin E1 expression; high-grade serous carcinoma; ovarian cancer; prognosis
Department(s): Laboratory Research
PubMed ID: 36572991
Publisher's Version: https://doi.org/10.1002/cncr.34582
Open Access at Publisher's Site: https://doi.org/10.1002/cncr.34582
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-06-27 07:58:59

Last Modified: 2023-06-27 07:59:22