Homologous recombination deficiency and cyclin E1 amplification are correlated with immune cell infiltration and survival in high-grade serous ovarian cancer

van Wagensveld, L. et al. (2022) Homologous recombination deficiency and cyclin E1 amplification are correlated with immune cell infiltration and survival in high-grade serous ovarian cancer. Cancers, 14(23), 5965. (doi: 10.3390/cancers14235965) (PMID:36497449) (PMCID:PMC9738162)

Abstract

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.

• Item Type: Articles
• Additional Information: This research was funded by the Dutch Cancer Society [IKNL2014-6838].
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Coffelt, Professor Seth
• Authors: van Wagensveld, L., van Baal, J. O. A. M., Timmermans, M., Gaillard, D., Borghuis, L., Coffelt, S. B., Rosenberg, E. H., Lok, C. A. R., Nijman, H. W., Kooreman, L. F. S., Sanders, J., de Bruijn, M., Wessels, L. F. A., van der Wiel, R., Rausch, C., Broeks, A., Kruitwagen, R. F. P. M., van der Aa, M. A., Sonke, G. S., Schouten, P. C., Van de Vijver, K. K., and Horlings, H. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: Cancers
• Publisher: MDPI
• ISSN: 2072-6694
• ISSN (Online): 2072-6694
• Published Online: 02 December 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Cancers 14(23): 5965
• Publisher Policy: Reproduced under a Creative Commons License