Association Between CD204-Expressed Tumor-Associated Macrophages and MGMT-Promoter Methylation in the Microenvironment of Grade 4 Astrocytomas
Copyright 2022, Kurdi et al..
Background: Tumor-associated macrophages (TAMs) are principal immune cells in glioma microenvironment which support tumor growth and proliferation. Our aim in this study was to assess the relationship between CD204-expressed TAMs and O6-methylguanine-DNA methyltransferase (MGMT)-promoter methylation in World Health Organization (WHO) grade 4 astrocytomas, and its impact on patient's clinical outcome.
Methods: The expression of CD204 + TAMs was quantitively assessed on 45 samples of WHO grade 4 astrocytomas using immunohistochemistry. MGMT-promoter methylation was tested by methylation techniques. The relationship between TAMs, MGMT-promoter methylation, and recurrence-free interval (RFI) was statistically analyzed.
Results: There were 10 cases (22.2%) with isocitrate dehydrogenase (IDH)-mutant grade 4 astrocytoma and 35 cases (77.8%) with IDH-wildtype glioblastoma. MGMT-promotor was methylated in 18 cases (40%), unmethylated in 15 cases (33%), and the remaining 12 cases showed no MGMT status because of nucleic acid degradations. The expression of CD204+ TAMs was high in 32 cases (71.7%) and low in 13 cases (28.8%). The relationship between IDH1 mutation and CD204+ TAM expression was insignificant (P = 0.93). However, the significant difference was found between MGMT methylation and CD204+ TAMs expression (P = 0.01), in which CD204+ TAMs were diffusely expressed in MGMT-methylated cases. There was no significant difference in RFI between CD204+ TAMs expression, MGMT-promoter methylation and treatment modalities.
Conclusions: Grade 4 astrocytomas with diffusely expressed CD204+ TAMs are usually associated with MGMT-promoter methylation. Although this association is unclear, CD204+ TAMs may neutralize the effect of MGMT-DNA protein to loss its function, which contributes to tumor progression. This relationship had no significant impact on the patient's clinical outcome after different treatment modalities.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
World journal of oncology - 13(2022), 3 vom: 15. Juni, Seite 117-125 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kurdi, Maher [VerfasserIn] |
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| Links: |
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| Themen: |
Astrocytoma |
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| Anmerkungen: |
Date Revised 16.07.2022 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.14740/wjon1473 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM343576236 |
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| 100 | 1 | |a Kurdi, Maher |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Association Between CD204-Expressed Tumor-Associated Macrophages and MGMT-Promoter Methylation in the Microenvironment of Grade 4 Astrocytomas |
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| 520 | |a Copyright 2022, Kurdi et al. | ||
| 520 | |a Background: Tumor-associated macrophages (TAMs) are principal immune cells in glioma microenvironment which support tumor growth and proliferation. Our aim in this study was to assess the relationship between CD204-expressed TAMs and O6-methylguanine-DNA methyltransferase (MGMT)-promoter methylation in World Health Organization (WHO) grade 4 astrocytomas, and its impact on patient's clinical outcome | ||
| 520 | |a Methods: The expression of CD204 + TAMs was quantitively assessed on 45 samples of WHO grade 4 astrocytomas using immunohistochemistry. MGMT-promoter methylation was tested by methylation techniques. The relationship between TAMs, MGMT-promoter methylation, and recurrence-free interval (RFI) was statistically analyzed | ||
| 520 | |a Results: There were 10 cases (22.2%) with isocitrate dehydrogenase (IDH)-mutant grade 4 astrocytoma and 35 cases (77.8%) with IDH-wildtype glioblastoma. MGMT-promotor was methylated in 18 cases (40%), unmethylated in 15 cases (33%), and the remaining 12 cases showed no MGMT status because of nucleic acid degradations. The expression of CD204+ TAMs was high in 32 cases (71.7%) and low in 13 cases (28.8%). The relationship between IDH1 mutation and CD204+ TAM expression was insignificant (P = 0.93). However, the significant difference was found between MGMT methylation and CD204+ TAMs expression (P = 0.01), in which CD204+ TAMs were diffusely expressed in MGMT-methylated cases. There was no significant difference in RFI between CD204+ TAMs expression, MGMT-promoter methylation and treatment modalities | ||
| 520 | |a Conclusions: Grade 4 astrocytomas with diffusely expressed CD204+ TAMs are usually associated with MGMT-promoter methylation. Although this association is unclear, CD204+ TAMs may neutralize the effect of MGMT-DNA protein to loss its function, which contributes to tumor progression. This relationship had no significant impact on the patient's clinical outcome after different treatment modalities | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Astrocytoma | |
| 650 | 4 | |a CD204 | |
| 650 | 4 | |a MGMT methylation | |
| 650 | 4 | |a Tumor-associated macrophages | |
| 700 | 1 | |a Katib, Yousef |e verfasserin |4 aut | |
| 700 | 1 | |a Faizo, Eyad |e verfasserin |4 aut | |
| 700 | 1 | |a Bahakeem, Basem |e verfasserin |4 aut | |
| 700 | 1 | |a Alkhotani, Alaa |e verfasserin |4 aut | |
| 700 | 1 | |a Alkhayyat, Shadi |e verfasserin |4 aut | |
| 700 | 1 | |a Najjar, Ahmed A |e verfasserin |4 aut | |
| 700 | 1 | |a Mehboob, Riffat |e verfasserin |4 aut | |
| 700 | 1 | |a Halawa, Taher F |e verfasserin |4 aut | |
| 700 | 1 | |a Addas, Bassam M J |e verfasserin |4 aut | |
| 700 | 1 | |a Albriky, Koloud |e verfasserin |4 aut | |
| 700 | 1 | |a Hakamy, Sahar |e verfasserin |4 aut | |
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