Homologous Recombination Deficiency and Cyclin E1 Amplification Are Correlated with Immune Cell Infiltration and Survival in High-Grade Serous Ovarian Cancer

Lilian van Wagensveld*, Juliette O A M van Baal, Maite Timmermans, Duco Gaillard, Lauri Borghuis, Seth B Coffelt, Efraim H Rosenberg, Christianne A R Lok, Hans W Nijman, Loes F S Kooreman, Joyce Sanders, Marco de Bruijn, Lodewyk F A Wessels, Rianne van der Wiel, Christian Rausch, Annegien Broeks, Roy F P M Kruitwagen, Maaike A van der Aa, Gabe S Sonke, Philip C SchoutenKoen K Van de Vijver, Hugo M Horlings

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND: How molecular profiles are associated with tumor microenvironment (TME) in high-grade serous ovarian cancer (HGSOC) is incompletely understood. Therefore, we analyzed the TME and molecular profiles of HGSOC and assessed their associations with overall survival (OS).

METHODS: Patients with advanced-stage HGSOC treated in three Dutch hospitals between 2008-2015 were included. Patient data were collected from medical records. BRCA1/2 mutation, BRCA1 promotor methylation analyses, and copy number variations were used to define molecular profiles. Immune cells were assessed with immunohistochemical staining.

RESULTS: 348 patients were categorized as BRCA mutation (BRCAm) (BRCAm or promotor methylation) (30%), non-BRCA mutated HRD (19%), Cyclin E1 (CCNE1)-amplification (13%), non-BRCAmut HRD and CCNE1-amplification (double classifier) (20%), and no specific molecular profile (NSMP) (18%). BRCAm showed highest immune cell densities and CCNE1-amplification lowest. BRCAm showed the most favorable OS (52.5 months), compared to non-BRCAmut HRD (41.0 months), CCNE1-amplification (28.0 months), double classifier (27.8 months), and NSMP (35.4 months). Higher immune cell densities showed a favorable OS compared to lower, also within the profiles. CD8+, CD20+, and CD103+ cells remained associated with OS in multivariable analysis.

CONCLUSIONS: Molecular profiles and TME are associated with OS. TME differs per profile, with higher immune cell densities showing a favorable OS, even within the profiles. HGSOC does not reflect one entity but comprises different entities based on molecular profiles and TME.

Original languageEnglish
Article number5965
Number of pages17
Issue number23
Publication statusPublished - 2 Dec 2022

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