CCNE1 and survival of patients with tubo‐ovarian high‐grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

Medientyp: E-Artikel
Titel: CCNE1 and survival of patients with tubo‐ovarian high‐grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study
Beteiligte: 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.; [...]
Erschienen: Wiley, 2023
Erschienen in: Cancer
Sprache: Englisch
DOI: 10.1002/cncr.34582
ISSN: 0008-543X; 1097-0142
Schlagwörter: Cancer Research ; Oncology
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Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>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 <jats:italic>CCNE1</jats:italic> 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 <jats:italic>CCNE1</jats:italic> and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>High‐level amplification (>8 copies by chromogenic <jats:italic>in situ</jats:italic> 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%. <jats:italic>CCNE1</jats:italic> 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, <jats:italic>p</jats:italic> = .034, and HR, 1.18; 95% CI, 1.05‐1.32, <jats:italic>p</jats:italic> = .015, respectively). This was also true for cases with combined high‐level amplification/overexpression (HR, 1.26; 95% CI, 1.09‐1.47, <jats:italic>p</jats:italic> = .033). <jats:italic>CCNE1</jats:italic> mRNA expression was not associated with overall survival (HR, 1.00 per 1‐SD increase; 95% CI, 0.94‐1.06; <jats:italic>p</jats:italic> = .58). <jats:italic>CCNE1</jats:italic> high‐level amplification is mutually exclusive with the presence of germline <jats:italic>BRCA1/2</jats:italic> pathogenic variants and shows an inverse association to RB1 loss.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>This study provides large‐scale validation that <jats:italic>CCNE1</jats:italic> high‐level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.</jats:p></jats:sec>

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