ArticleThe journal of pathology. Clinical research2020
Combined CCNE1 high-level amplification and overexpression is associated with unfavourable outcome in tubo-ovarian high-grade serous carcinoma.
Article in The journal of pathology. Clinical research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Morphological and molecular characterization of epithelial ovarian cancer: SEOM-SEAP consensus guidelines for biomarker integration in clinical practice.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Guideline
- A chemoresistance-associated proliferation gene signature identified by single-cell and machine learning analysis predicts prognosis in high-grade serous ovarian carcinoma.Translational oncology · 2026Article
- CCNE1 overexpression drives a cGAS-STING-dependent interferon response and sensitizes HRD-positive ovarian cancer to immune checkpoint blockade.Journal for immunotherapy of cancer · 2026Article
- CCNE1: A Cell Cycle Regulator That Influences Tumor Progression.Cancer medicine · 2026Review
- Lethal clinical outcome and immune desert contexture in refractory gastric cancer harboring CCNE1 amplification and overexpression.British journal of cancer · 2026Article
- Changes in Cyclin E1 expression and CCNE1 amplification in high-grade ovarian carcinomas post-PARP inhibitor exposure.British journal of cancer · 2026Article
- Cyclin E1 overexpression identifies a therapeutically relevant poor prognostic patient subgroup in high-grade serous ovarian cancer.NPJ precision oncology · 2026Article
- Models of high-grade serous carcinoma of tubo-ovarian origin.Oncology reviews · 2026Review
- Article
- Context is key: how diagnostic and prognostic markers are reshaping gynecologic pathology.The journal of pathology. Clinical research · 2025Review
- Leveraging Real-World Data From a Clinicogenomic Database Addresses the Treatment Gap in Patients With High-Grade Serous Ovarian Cancer.JCO precision oncology · 2025Observational
- Comparative Analysis of Gene Expression Analysis Methods for RNA in Situ Hybridization Images.The Journal of molecular diagnostics : JMD · 2024Article
- Targeted and Shallow Whole-Genome Sequencing Identifies Therapeutic Opportunities in p53abn Endometrial Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Compartment-specific multiomic profiling identifies SRC and GNAS as candidate drivers of epithelial-to-mesenchymal transition in ovarian carcinosarcoma.British journal of cancer · 2024Article
- Adavosertib Enhances Antitumor Activity of Trastuzumab Deruxtecan in HER2-Expressing Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study.The journal of pathology. Clinical research · 2023Article
- Article
- The Roles of Exosomes in Ovarian Cancer Chemo-resistance.Journal of Cancer · 2023Review
- Diagnostics and treatment of ovarian cancer in the era of precision medicine - opportunities and challenges.Frontiers in oncology · 2023Review
- Multiparameter single-cell proteomic technologies give new insights into the biology of ovarian tumors.Seminars in immunopathology · 2023Review
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
CCNE1 amplification is a recurrent alteration associated with unfavourable outcome in tubo-ovarian high-grade serous carcinoma (HGSC). We aimed to investigate whether immunohistochemistry (IHC) can be used to identify CCNE1 amplification status and to validate whether CCNE1 high-level amplification and overexpression are prognostic in HGSC. A testing set of 528 HGSC samples stained with two optimised IHC assays (clones EP126 and HE12) was subjected to digital image analysis and visual scoring. DNA and RNA chromogenic in situ hybridisation for CCNE1 were performed. IHC cut-off was determined by receiver operating characteristics (ROC). Survival analyses (endpoint ovarian cancer specific survival) were performed and validated in an independent validation set of 764 HGSC. Finally, combined amplification/expression status was evaluated in cases with complete data (n = 1114). CCNE1 high-level amplification was present in 11.2% of patients in the testing set and 10.2% in the combined cohort. The optimal cut-off for IHC to predict CCNE1 high-level amplification was 60% positive tumour cells with at least 5% strong staining cells (sensitivity 81.6%, specificity 77.4%). CCNE1 high-level amplification and overexpression were associated with survival in the testing and validation set. Combined CCNE1 high-level amplification and overexpression was present in 8.3% of patients, mutually exclusive to germline BRCA1/2 mutation and significantly associated with a higher risk of death in multivariate analysis adjusted for age, stage and cohort (hazard ratio = 1.78, 95 CI% 1.38-2.26, p < 0.0001). CCNE1 high-level amplification combined with overexpression identifies patients with a sufficiently poor prognosis that treatment alternatives are urgently needed. Given that this combination is mutually exclusive to BRCA1/2 germline mutations, a predictive marker for PARP inhibition, CCNE1 high-level amplification combined with overexpression may serve as a negative predictive test for sensitivity to PARP inhibitors.
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