CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.
Date
2023-03-01Author
Kang, E-Y
Weir, A
Meagher, NS
Farrington, K
Nelson, GS
Ghatage, P
Lee, C-H
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
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
AOCS Group,
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, FKF
Kruitwagen, RFPM
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
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
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, PA
Goode, EL
Goodman, MT
Gronwald, J
Karlan, BY
Kommoss, S
Menon, U
Sinn, H-P
Staebler, A
Brenton, JD
Bowtell, DD
Pharoah, PDP
Ramus, SJ
Köbel, M
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
CCNE1 amplification
cyclin E1 expression
high-grade serous carcinoma
ovarian cancer
prognosis
Female
Humans
Ovarian Neoplasms
Transcription Factors
Carcinoma
RNA, Messenger
Cystadenocarcinoma, Serous
Oncogene Proteins
Cyclin E
Research team
Aetiological Epidemiology
Language
eng
Date accepted
2022-09-30
License start date
2023-03-01
Citation
Cancer, 2023, 129 (5), pp. 697 - 713
Publisher
WILEY