Citations 2
CCNE1 and survival of patients with tubo‐ovarian high‐grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study
Kang, Eunyoung , Weir, Ashley , Meagher, Nicola S. , Farrington, Kyo , Nelson, Gregg , Lee, Cheng‐Han , Riggan, Marjorie J. , Popović, Gordana , Leung, Betty, Tang, Katrina , Lambie, Neil, Millstein, Joshua , Alsop, Jennifer , Anglesio, Michael S. , Barlow, Ellen , Beckmann, Matthias W. , Berger, Jessica, Bisinotto, Christiani, Bösmüller, Hans , Boros, Jessica , Brand, Alison H. , Carney, Michael E. , Casablanca, Yovanni , Cohen, Paul A. , Coulson, Penny , Courtney‐Brooks, Madeleine , Cunningham, Julie M. , Darcy, Kathleen M. , El‐Bahrawy, Mona A., Farrell, Rhonda , Fischer, Anna , García, María J. , Gayther, Simon A. , Group, AOCS, Harnett, Paul R. , Harrington, Shariska P. , Harter, Philipp , Hartmann, Arndt , Hecht, Jonathan L. , Heikaus, Sebastian, Hendley, Joy , Polo, Susanna Hernando, Heublein, Sabine , Hirasawa, Akira , Huntsman, David G. , Jimenez‐Liñan, Mercedes , Jones, Michael E. , Kennedy, Catherine J. , Khabele, Dineo , Lambrechts, Diether , Le, Nhu D. , Lener, Marcin , Lester, Jenny , Leung, Yee , Linder, Anna , Loverix, Liselore , Madan, Rashna , Maxwell, G. Larry , Olawaiye, Alexander , Oršulić, Sandra , Palacios, José , Pearce, Celeste Leigh , Pike, Malcolm C. , Quinn, Carmel M. , Mohan, Ganendra Raj , Rodríguez‐Antona, Cristina , Ruebner, Matthias , Ryan, Andy , Salfinger, Stuart , Sasamoto, Naoko , Schildkraut, Joellen M. , Schoemaker, Minouk J. , Shah, Mitul , Sharma, Raghwa , Shvetsov, Yurii B. , Singh, Naveena , Steele, Linda , Stewart, Colin J.R. , Talhouk, Aline , Tan, Adeline , Terry, Kathryn L. , Tołoczko, Aleksandra, Aa, Maaike A. van der , Gorp, Toon Van , Nieuwenhuysen, Els Van , van‐Wagensveld, Lilian, Vergote, Ignace , Wu, Anna H. , Reis, Francisco José Cândido dos , Fasching, Peter A. , Goode, Ellen L. , Goodman, Marc T. , Kommoss, Stefan , Menon, Usha , Sinn, Hans‐Peter , Staebler, Annette , Bowtell, David D.L. , Ramus, Susan J. , Lambrechts, Diether , El‐Bahrawy, Mona , Lee, Cheng-Han , Fereday, Sian , Kennedy, Catherine J , Sasamoto, Naoko , Schildkraut, Joellen M , Talhouk, Aline , Vergote, Ignace , Köbel, Martin , Lambrechts, Diether , Ramus, Susan J , Rodríguez-Antona, Cristina , Menon, Usha , Sinn, Peter , Anglesio, Michael S , Jones, Michael E , Lambrechts, Diether , Brand, Alison H , Bowtell, David D , Nelson, Gregg S , El-Bahrawy, Mona A , Harnett, Paul R , Schoemaker, Minouk J , Goodman, Marc T , Linder, Anna , Cohen, Paul , Kang, Eun‐Young, Ghatage, Prafull , Bolithon, Adelyn , Ataseven, Beyhan , Brooks‐Wilson, Angela , Brucker, Sara Yvonne , Cazorla, Alicia , Conrads, Thomas , Cook, Linda S. , Cramer, Daniel W. , Crowe, Philip John , Cybulski, Cezary , Elishaev, Esther , Erber, Ramona , Fereday, Sián , Gentry‐Maharaj, Aleksandra , Gilks, C. Blake , Group, AOCS, Grube, Marcel , Hein, Alexander , Heitz, Florian , Hernandez, Brenda Y. , Høgdall, Estrid , Høgdall, Claus , Horlings, Hugo , Huzarski, Tomasz , Jewell, Andrea , Kaufmann, Scott H. , Kommoss, Felix , Kruitwagen, Roy F.P.M. , Lubiński, Jan , Modugno, Francesmary , Neuhausen, Susan L. , Olbrecht, Siel , Sonke, Gabe S. , Sundfeldt, Karin , Swerdlow, Anthony J. , Taylor, Sarah E. , Traficante, Nadia , Van de Vijver, Koen , Vierkant, Robert A. , Wang, Chen , Wilkens, Lynne R. , Winham, Stacey J. , Benı́tez, Javier , Berchuck, Andrew , DeFazio, Anna , Gronwald, Jacek , Karlan, Beth Y. , Brenton, James D. , Pharoah, Paul D.P. , Köbel, Martin
Cancer | December 27, 2022 | Volume: 129 | Issue: 5 | Pages: 697-713
AbstractBackgroundCyclin 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.
Dilution of Molecular–Pathologic Gene Signatures by Medically Associated Factors Might Prevent Prediction of Resection Status After Debulking Surgery in Patients With Advanced Ovarian Cancer
Kommoss, Stefan , Tourani, Roshan , Grandelis, Anthony , Uppendahl, Locke , Aliferis, Constantin , Burges, Alexander , Wang, Chen , Canzler, Ulrich , Belau, Antje , Prader, Sonia , Hanker, Lars , Ma, Sisi , Hilpert, Felix , Schneider, Stephanie , Kimmig, Rainer , Kurzeder, Christian , Schmalfeldt, Barbara , Braicu, Elena Ioana , Harter, Philipp , Dowdy, Sean C. , Winterhoff, Boris , Pfisterer, Jacobus , Uppendahl, Locke , Burges, Alexander , Wang, Chen , Heitz, Florian , Ma, Sisi , Ataseven, Beyhan , Sehouli, Jalid , Bois, Andreas du
Clinical Cancer Research | September 16, 2019 | Volume: 26 | Issue: 1 | Pages: 213-219
Abstract Purpose: Predicting surgical outcome could improve individualizing treatment strategies for patients with advanced ovarian cancer. It has been suggested earlier that gene expression signatures (GES) might harbor the potential to predict surgical outcome. Experimental Design: Data derived from high-grade serous tumor tissue of FIGO stage IIIC/IV patients of AGO-OVAR11 trial were used to generate a transcriptome profiling. Previously identified molecular signatures were tested. A theoretical model was implemented to evaluate the impact of medically associated factors for residual disease (RD) on the performance of GES that predicts RD status. Results: A total of 266 patients met inclusion criteria, of those, 39.1% underwent complete resection. Previously reported GES did not predict RD in this cohort. Similarly, The Cancer Genome Atlas molecular subtypes, an independent de novo signature and the total gene expression dataset using all 21,000 genes were not able to predict RD status. Medical reasons for RD were identified as potential limiting factors that impact the ability to use GES to predict RD. In a center with high complete resection rates, a GES which would perfectly predict tumor biological RD would have a performance of only AUC 0.83, due to reasons other than tumor biology. Conclusions: Previously identified GES cannot be generalized. Medically associated factors for RD may be the main obstacle to predict surgical outcome in an all-comer population of patients with advanced ovarian cancer. If biomarkers derived from tumor tissue are used to predict outcome of patients with cancer, selection bias should be focused on to prevent overestimation of the power of such a biomarker. See related commentary by Handley and Sood, p. 9