| Authors: |
Kang, E. Y.; Weir, A.; Meagher, N. S.; Farrington, K.; Nelson, G. S.; Ghatage, P.; Lee, C. H.; Riggan, M. J.; Bolithon, A.; Popovic, G.; Leung, B.; Tang, K.; Lambie, N.; Millstein, J.; Alsop, J.; Anglesio, M. S.; Ataseven, B.; Barlow, E.; Beckmann, M. W.; Berger, J.; Bisinotto, C.; Bösmüller, H.; Boros, J.; Brand, A. H.; Brooks-Wilson, A.; Brucker, S. Y.; Carney, M. E.; Casablanca, Y.; Cazorla-Jiménez, A.; Cohen, P. A.; Conrads, T. P.; Cook, L. S.; Coulson, P.; Courtney-Brooks, M.; Cramer, D. W.; Crowe, P.; Cunningham, J. M.; Cybulski, C.; Darcy, K. M.; El-Bahrawy, M. A.; Elishaev, E.; Erber, R.; Farrell, R.; Fereday, S.; Fischer, A.; García, M. J.; Gayther, S. A.; Gentry-Maharaj, A.; Gilks, C. B.; AOCS Group; Grube, M.; Harnett, P. R.; Harrington, S. P.; Harter, P.; Hartmann, A.; Hecht, J. L.; Heikaus, S.; Hein, A.; Heitz, F.; Hendley, J.; Hernandez, B. Y.; Polo, S. H.; Heublein, S.; Hirasawa, A.; Høgdall, E.; Høgdall, C. K.; Horlings, H. M.; Huntsman, D. G.; Huzarski, T.; Jewell, A.; Jimenez‐Linan, M.; Jones, M. E.; Kaufmann, S. H.; Kennedy, C. J.; Khabele, D.; Kommoss, F. K. F.; Kruitwagen, R. F. P. M.; Lambrechts, D.; Le, N. D.; Lener, M.; Lester, J.; Leung, Y.; Linder, A.; Loverix, L.; LubińskI, J.; Madan, R.; Maxwell, G. L.; Modugno, F.; Neuhausen, S. L.; Olawaiye, A.; Olbrecht, S.; Orsulic, S.; Palacios, J.; Pearce, C. L.; Pike, M. C.; DPhil, C. M. Q.; Mohan, G. R.; Rodríguez‐Antona, C.; Ruebner, M.; Ryan, A.; Salfinger, S. G.; Sasamoto, N.; Schildkraut, J. M.; Schoemaker, M. J.; Shah, M.; Sharma, R.; Shvetsov, Y. B.; Singh, N.; Sonke, G. S.; Steele, L.; Stewart, C. J. R.; Sundfeldt, K.; Swerdlow, A. J.; Talhouk, A.; Tan, A.; Taylor, S. E.; Terry, K. L.; Tołoczko, A.; Traficante, N.; Van de Vijver, K. K.; van der Aa, M. A.; Van Gorp, T.; Nieuwenhuysen, E. V.; van‐Wagensveld, L.; Vergote, I.; Vierkant, R. A.; Wang, C.; Wilkens, L. R.; Winham, S. J.; Wu, A. H.; Benitez, J.; Berchuck, A.; Candido dos Reis, F. J.; DeFazio, A.; Fasching. P. A.; Goode, E. L.; Goodman, M. T.; Gronwald, J.; Karlan, B. Y.; Kommoss, S.; Menon, U.; Sinn, H. P.; Staebler, A.; Brenton, J. D.; Bowtell, D. D.; Pharoah, P. D. P.; Ramus, S. J.; Köbel, M. |
| Article Title: |
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. © 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society. |
| Keywords: |
immunohistochemistry; adult; cancer survival; human tissue; protein expression; aged; middle aged; survival analysis; young adult; unclassified drug; major clinical study; overall survival; adjuvant therapy; cancer staging; ovarian cancer; cytoreductive surgery; gene overexpression; gene amplification; cohort analysis; genetic association; genetic variability; brca1 protein; brca2 protein; age; tumor suppressor gene; messenger rna; ovary carcinoma; gene loss; hazard ratio; platinum complex; retinoblastoma protein; cyclin e; germline mutation; fallopian tube carcinoma; high-grade serous carcinoma; cyclin e1; chromogenic in situ hybridization; very elderly; prognosis; human; female; article; ccne1 amplification; cyclin e1 expression; tuboovarian high grade serous carcinoma
|
| Journal Title: |
Cancer
|
| Volume: |
129 |
| Issue: |
5 |
| ISSN: |
0008-543X |
| Publisher: |
Wiley Blackwell
|
| Date Published: |
2023-03-01 |
| Start Page: |
697 |
| End Page: |
713 |
| Language: |
English |
| DOI: |
10.1002/cncr.34582
|
| PROVIDER: |
scopus
|
| PUBMED: |
36572991
|
| PMCID: |
PMC10107112
|
| DOI/URL: |
|
| Notes: |
Article -- Export Date: 1 March 2023 -- Source: Scopus |
