Homologous Recombination Deficiency and Cyclin E1 Amplification Are Correlated with Immune Cell Infiltration and Survival in High-Grade Serous Ovarian Cancer
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Cancers - 14(2022), 23 vom: 02. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
van Wagensveld, Lilian [VerfasserIn] |
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| Links: |
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| Themen: |
Epithelial ovarian carcinoma |
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| Anmerkungen: |
Date Revised 21.12.2022 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/cancers14235965 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM350096538 |
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| 100 | 1 | |a van Wagensveld, Lilian |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Homologous Recombination Deficiency and Cyclin E1 Amplification Are Correlated with Immune Cell Infiltration and Survival in High-Grade Serous Ovarian Cancer |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Revised 21.12.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a epithelial ovarian carcinoma | |
| 650 | 4 | |a homologous | |
| 650 | 4 | |a microenvironment | |
| 650 | 4 | |a ovarian neoplasms/genetics | |
| 650 | 4 | |a prognosis | |
| 650 | 4 | |a recombination | |
| 650 | 4 | |a tumor | |
| 700 | 1 | |a van Baal, Juliette O A M |e verfasserin |4 aut | |
| 700 | 1 | |a Timmermans, Maite |e verfasserin |4 aut | |
| 700 | 1 | |a Gaillard, Duco |e verfasserin |4 aut | |
| 700 | 1 | |a Borghuis, Lauri |e verfasserin |4 aut | |
| 700 | 1 | |a Coffelt, Seth B |e verfasserin |4 aut | |
| 700 | 1 | |a Rosenberg, Efraim H |e verfasserin |4 aut | |
| 700 | 1 | |a Lok, Christianne A R |e verfasserin |4 aut | |
| 700 | 1 | |a Nijman, Hans W |e verfasserin |4 aut | |
| 700 | 1 | |a Kooreman, Loes F S |e verfasserin |4 aut | |
| 700 | 1 | |a Sanders, Joyce |e verfasserin |4 aut | |
| 700 | 1 | |a de Bruijn, Marco |e verfasserin |4 aut | |
| 700 | 1 | |a Wessels, Lodewyk F A |e verfasserin |4 aut | |
| 700 | 1 | |a van der Wiel, Rianne |e verfasserin |4 aut | |
| 700 | 1 | |a Rausch, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Broeks, Annegien |e verfasserin |4 aut | |
| 700 | 1 | |a Kruitwagen, Roy F P M |e verfasserin |4 aut | |
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| 700 | 1 | |a Horlings, Hugo M |e verfasserin |4 aut | |
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