CCNE1 Amplification as a Candidate Marker of Homologous Recombination Proficiency in High-Grade Serous Ovarian Cancer: A Scoping Review

Abstract

BACKGROUND: Homologous recombination proficiency (HRP) high-grade serous ovarian cancer (HGSOC) is molecularly heterogeneous and lacks validated biomarkers for patient stratification. CCNE1 amplification has been associated with molecular profiles indicative of HRP-like molecular profiles, but it is unclear whether this reflects actual functional homologous recombination (HR) repair capacity, or how consistently the association holds across different definitions of CCNE1 and HR status. This scoping review mapped the evidence linking CCNE1 copy-number alteration and cyclin E1 overexpression with HR-related molecular features in.

METHODS: A scoping review was following the Arksey and O’Malley framework and PRISMA-ScR. PubMed, Scopus, ProQuest, and Springer Nature were searched from inception to October 1, 2026 for original human studies examining CCNE1 amplification, copy-number gain, or cyclin E1 overexpression in relation to HR-related features in HGSOC. CCNE1 and HR-status definitions and the reported relationships were charted and synthesized descriptively.

RESULTS: Sixteen studies published between 2013 and 2026 were included. One amplification thresholds ranged from an average copy number above 2.0 to more than 8 copies per cell, and HR status was defined by BRCA1/2 testing or by genomic HR deficiency (HRD) scores with differing cut-offs. Eleven studies reported a mutually exclusive between 1 amplification and BRCA1/2 alterations or HRD-associated features, most consistently for high-level amplification versus pathogenic BRCA1/2 variants; one reported a non-significant inverse trend. Four reported co-occurrences, mainly with low-level gain, broad alteration categories, copy-number-based HRD classifiers, or very small samples. Cyclin E1 overexpression and CCNE1 amplification were related but non-equivalent biomarkers. Evidence from Asian populations only came from a single Japanese cohort.

CONCLUSION: High-level CCNE1 amplification is preferentially associated with an HRP-like molecular profiles, but current evidence does not establish its validity as a candidate marker for HRP. Standardized, cross-platform validation, comparison with functional HR assays, and validation in underrepresented populations, including Asian cohorts, are needed before CCNE1 can be evaluated as a complementary pathology-based marker.

KEYWORDS: high-grade serous ovarian cancer, CCNE1, cyclin E1, homologous recombination status, biomarker