TY - JOUR
T1 - Homologous Recombination Deficiency and Cyclin E1 Amplification Are Correlated with Immune Cell Infiltration and Survival in High-Grade Serous Ovarian Cancer
AU - van Wagensveld, Lilian
AU - van Baal, Juliette O A M
AU - Timmermans, Maite
AU - Gaillard, Duco
AU - Borghuis, Lauri
AU - Coffelt, Seth B
AU - Rosenberg, Efraim H
AU - Lok, Christianne A R
AU - Nijman, Hans W
AU - Kooreman, Loes F S
AU - Sanders, Joyce
AU - de Bruijn, Marco
AU - Wessels, Lodewyk F A
AU - van der Wiel, Rianne
AU - Rausch, Christian
AU - Broeks, Annegien
AU - Kruitwagen, Roy F P M
AU - van der Aa, Maaike A
AU - Sonke, Gabe S
AU - Schouten, Philip C
AU - Van de Vijver, Koen K
AU - Horlings, Hugo M
N1 - Funding Information:
This research was funded by the Dutch Cancer Society [IKNL2014-6838].
Funding Information:
We acknowledge the NKI-AVL Core Facility Molecular Pathology & Biobanking for supplying NKI-AVL Biobank material and lab support. We also acknowledge institutional funding from the Dutch Cancer Society and support from the Research High Performance Computing facility.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/12/2
Y1 - 2022/12/2
N2 - 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.
AB - 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.
U2 - 10.3390/cancers14235965
DO - 10.3390/cancers14235965
M3 - Article
C2 - 36497449
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 23
M1 - 5965
ER -