| Title: |
CCNE1 and survival of patients with tubo‐ovarian high‐grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study |
| Authors: |
Kang, Eun‐Young; Kang, Eun‐Young; Weir, Ashley; Meagher, Nicola S; Farrington, Kyo; Nelson, Gregg S; Ghatage, Prafull; Lee, Cheng‐Han; Riggan, Marjorie J; Bolithon, Adelyn; Popovic, Gordana; Leung, Betty; Tang, Katrina; Lambie, Neil; Millstein, Joshua; Alsop, Jennifer; Anglesio, Michael S; Ataseven, Beyhan; Barlow, Ellen; Beckmann, Matthias W; Berger, Jessica; Bisinotto, Christiani; Bösmüller, Hans; Boros, Jessica; Brand, Alison H; Brooks‐Wilson, Angela; Brucker, Sara Y; Carney, Michael E; Casablanca, Yovanni; Cazorla‐Jiménez, Alicia; Cohen, Paul A; Conrads, Thomas P; Cook, Linda S; Coulson, Penny; Courtney‐Brooks, Madeleine; Cramer, Daniel W; Crowe, Philip; Cunningham, Julie M; Cybulski, Cezary; Darcy, Kathleen M; El‐Bahrawy, Mona A; Elishaev, Esther; Erber, Ramona; Farrell, Rhonda; Fereday, Sian; Fischer, Anna; García, María J; Gayther, Simon A; Gentry‐Maharaj, Aleksandra; Gilks, C Blake; Group, AOCS; Grube, Marcel; Harnett, Paul R; Harrington, Shariska Petersen; Harter, Philipp; Hartmann, Arndt; Hecht, Jonathan L; Heikaus, Sebastian; Hein, Alexander; Heitz, Florian; Hendley, Joy; Hernandez, Brenda Y; Polo, Susanna Hernando; Heublein, Sabine; Hirasawa, Akira; Høgdall, Estrid; Høgdall, Claus K; Horlings, Hugo M; Huntsman, David G; Huzarski, Tomasz; Jewell, Andrea; Jimenez‐Linan, Mercedes; Jones, Michael E; Kaufmann, Scott H; Kennedy, Catherine J; Khabele, Dineo; Kommoss, Felix KF; Kruitwagen, Roy FPM; Lambrechts, Diether; Le, Nhu D; Lener, Marcin; Lester, Jenny; Leung, Yee; Linder, Anna; Loverix, Liselore; Lubiński, Jan; Madan, Rashna; Maxwell, G Larry; Modugno, Francesmary; Neuhausen, Susan L; Olawaiye, Alexander; Olbrecht, Siel; Orsulic, Sandra; Palacios, José; Pearce, Celeste Leigh; Pike, Malcolm C; Quinn, Carmel M; Mohan, Ganendra Raj; Rodríguez‐Antona, Cristina; Ruebner, Matthias; Ryan, Andy |
| Source: |
Cancer; vol 129, iss 5, 697-713; 0008-543X |
| Publisher Information: |
eScholarship, University of California 2023-03-01 |
| Document Type: |
Electronic Resource |
| Abstract: |
BackgroundCyclin 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.MethodsWithin the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated.ResultsHigh-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.ConclusionThis study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC. |
| Index Terms: |
Clinical Research; Rare Diseases; Ovarian Cancer; Cancer; Aetiology; 2.1 Biological and endogenous factors; Female; Humans; Ovarian Neoplasms; Transcription Factors; Carcinoma; RNA; Messenger; Cystadenocarcinoma; Serous; Oncogene Proteins; Cyclin E; CCNE1 amplification; cyclin E1 expression; high-grade serous carcinoma; ovarian cancer; prognosis; AOCS Group; Oncology and Carcinogenesis; Public Health and Health Services; Oncology & Carcinogenesis; article |
| URL: |
https://escholarship.org/uc/item/6cm6k1w1; https://escholarship.org/ |
| Availability: |
Open access content. Open access content; CC-BY |
| Note: |
application/pdf; Cancer vol 129, iss 5, 697-713 0008-543X |
| Other Numbers: |
CDLER oai:escholarship.org:ark:/13030/qt6cm6k1w1; qt6cm6k1w1; https://escholarship.org/uc/item/6cm6k1w1; https://escholarship.org/; 1401039062 |
| Contributing Source: |
UC MASS DIGITIZATION; From OAIster®, provided by the OCLC Cooperative. |
| Accession Number: |
edsoai.on1401039062 |
| Database: |
OAIster |