World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access
Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc
Journal website https://www.wjon.org

Original Article

Volume 13, Number 3, June 2022, pages 117-125


Association Between CD204-Expressed Tumor-Associated Macrophages and MGMT-Promoter Methylation in the Microenvironment of Grade 4 Astrocytomas

Figures

Figure 1.
Figure 1. CD204+ TAMs expression in WHO grade 4 astrocytoma using IHC. (a) CD204+ TAMs high expression. (b) CD204+ TAMs low expression. (c) Normal brain control. (d) Diagram shows the relationship between TAMs and tumor cells. Magnification (× 100 µm). TAMs: tumor-associated macrophages; WHO: World Health Organization; IHC: immunohistochemistry.
Figure 2.
Figure 2. The relationship between CD204+ TAMs expression and MGMT-promoter methylation with RFI in WHO grade 4 astrocytoma patients. KM graphs show no statistically significant difference in RFI between CD204+ TAMs expression and MGMT-promoter methylation using different treatment modalities. TAMs: tumor-associated macrophages; MGMT: O6-methylguanine-DNA methyltransferase; RFI: recurrence-free interval; WHO: World Health Organization; KM: Kaplan-Meier.

Tables

Table 1. Demographic Data of 45 Cases of WHO Grade 4 Astrocytoma Enrolled in the Study
 
Overall (n = 45)
IDH: isocitrate dehydrogenase; MGMT: O6-methylguanine-DNA methyltransferase; TAMs: tumor-associated macrophages; WHO: World Health Organization.
Age
  < 55 years10 (22%)
  ≥ 55 years35 (78%)
IDH status
  IDH-wildtype35 (77.8%)
  IDH-mutant10 (22.2%)
Genetic profile
  Unmethylated MGMT15 (33.3%)
  Methylated MGMT18 (40%)
  Unknown12 (26.6%)
Tumor location
  Frontal18 (40%)
  Temporal12 (26.6%)
  Parietal12 (26.6%)
  Occipital2 (4.4%)
  Cerebellar1 (2.2%)
CD204+ TAMs expression
  High expression32 (71.1%)
  Low expression13 (28.8%)
Adjuvant therapy
  Chemoradiotherapy26 (57.7%)
  Radiation17 (37.7%)
  None2 (4.6%)

 

Table 2. Patients’ Data Enrolled in This Study
 
AgeGenderLocationIDH1ATRXCD204MGMTAdjuvantCTRFI
Data include age, gender, tumor location, IDH1 status, MGMT-promoter methylation, CD204+ TAM expression, treatment modalities, and RFI. All the enrolled cases were WHO grade 4 astrocytomas that presented with necrosis, microvascular proliferations, ATRX loss and intact 1p19q. IDH-w: IDH-wildtype; IDH-m: IDH-mutant; MGMT: O6-methylguanine-DNA methyltransferase; RT: radiotherapy; CT: chemotherapy; TMZ: temozolomide; RFI: recurrence-free interval.
50MaleFrontalIDH-mLossHighMethylatedRTNone670
66MaleFrontalIDH-mLossLowMethylatedCT + RTTMZ1,034
71MaleParietalIDH-mLossHighMethylatedCT + RTTMZ440
31FemaleParietalIDH-mLossHighUnknownRTNone670
64FemaleParietalIDH-mLossHighUnmethylatedCT + RTTMZ+731
57MaleParietalIDH-mLossLowMethylatedCT + RTTMZ+1,096
63MaleCerebellarIDH-mLossHighUnknownCT + RTTMZ+1,123
72FemaleFrontalIDH-mLossLowUnmethylatedRTNone643
69FemaleParietalIDH-mLossHighMethylatedRTNone638
58FemaleTemporalIDH-mLossHighUnmethylatedCT + RTTMZ801
19MaleFrontalIDH-wLossLowUnknownRTNone330
58MaleFrontalIDH-wLossLowUnmethylatedRTNone530
28FemaleParietalIDH-wLossLowUnmethylatedCT + RTTMZ330
22MaleTemporalIDH-wLossHighUnknownRTNone250
63MaleFrontalIDH-wLossHighUnmethylatedRTNone430
68MaleFrontalIDH-wLossHighMethylatedCT + RTTMZ1,016
59MaleTemporalIDH-wLossHighUnmethylatedRTNone293
73FemaleParietalIDH-wLossHighMethylatedCT + RTTMZ+156
76FemaleFrontalIDH-wLossHighUnknownCT + RTTMZ150
46FemaleOccipitalIDH-wLossLowUnmethylatedRTNone183
63FemaleTemporalIDH-wLossHighUnknownCT + RTTMZ194
82MaleFrontalIDH-wLossHighMethylatedCT + RTTMZ+340
57FemaleParietalIDH-wLossHighMethylatedCT + RTTMZ+260
10MaleTemporalIDH-wLossLowMethylatedNoneNone92
42MaleFrontalIDH-wLossHighUnknownCT + RTTMZ306
59FemaleOccipitalIDH-wLossHighMethylatedCT + RTTMZ+826
64MaleFrontalIDH-wLossHighMethylatedRTNone273
63MaleTemporalIDH-wLossLowUnmethylatedRTNone550
47MaleTemporalIDH-wLossHighUnknownRTNone141
62FemaleFrontalIDH-wLossLowUnmethylatedRTNone90
69MaleTemporalIDH-wLossHighUnknownNoneNone114
59FemaleFrontalIDH-wLossHighMethylatedCT + RTTMZ0
17MaleFrontalIDH-wLossHighMethylatedCT + RTTMZ+460
68MaleTemporalIDH-wLossHighUnmethylatedCT + RTTMZ311
61FemaleTemporalIDH-wLossLowUnmethylatedCT + RTTMZ+853
56MaleParietalIDH-wLossHighUnmethylatedCT + RTTMZ174
55MaleFrontalIDH-wLossHighUnknownCT + RTTMZ+200
70MaleFrontalIDH-wLossHighMethylatedCT + RTTMZ+730
76MaleFrontalIDH-wLossLowUnmethylatedCT + RTTMZ169
61MaleTemporalIDH-wLossHighMethylatedCT + RTTMZ191
76MaleParietalIDH-wLossHighUnknownRTNone128
62MaleTemporalIDH-wLossLowUnmethylatedCT + RTTMZ555
73FemaleParietalIDH-wLossHighUnknownRTNone195
57FemaleFrontalIDH-wLossHighMethylatedCT + RTTMZ288
81MaleParietalIDH-wLossHighMethylatedRTNone59

 

Table 3. Primers for MS-PCR Used for the Assessment of MGMT-Promoter Methylation
 
PrimerSequence
MS-PCR: methylation specific-polymerase chain reaction; MGMT: O6-methylguanine-DNA methyltransferase.
MSP-MGMT-MetF5′-TTTCGACGTTCGTAGGTTTTCGC-3′
MSP-MGMT-MetR5′-GCACTCTTCCGAAAACGAAACG-3′
MSP-MGMT-UnMetF5′-TTTGTGTTTTGATGTTTGTAGGTTTTTGT-3′
MSP-MGMT-UnMetR5′-AACTCCACACTCTTCCAAAAACAAAACA-3′

 

Table 4. Relationship Between CD204+ TAMs and MGMT-Promoter Methylation
 
CD204+ TAMsMGMT-promoter profileP-value
Unmethylated, n (%)Methylated, n (%)
MGMT: O6-methylguanine-DNA methyltransferase; TAMs: tumor-associated macrophages.
High expression6 (28.5%)15 (71.6%)0.01
Low expression9 (75%)3 (25%)

 

Table 5. Relationship Between CD204+ TAMs and IDH Mutation
 
CD204+ TAMsIDH mutationP-value
IDH-mutant, n (%)IDH-wildtype, n (%)
IDH: isocitrate dehydrogenase; TAMs: tumor-associated macrophages.
High expression7 (21.8%)25 (78.2%)0.93
Low expression3 (23.1%)10 (76.9%)

 

Table 6. Relationship Between CD204+ TAMs, MGMT methylation and RFI
 
MeanMedian
EstimateStandard error95% confidence intervalEstimateStandard error95% confidence interval
Lower boundUpper boundLower bound
MGMT: O6-methylguanine-DNA methyltransferase; TAMs: tumor-associated macrophages; RI: recurrence interval; RFI: recurrence-free interval.
RI
CD204 high
  MGMT methylation423.13376.467273.258573.009340.000107.558129.186
  Non-methylation456.667103.673253.468659.865311.00083.895146.566
  Overall432.71460.851313.447551.982340.000104.517135.147
RFI
CD204 low
  MGMT methylation740.667324.827104.0061,377.3271,034.000769.1400.000
  Non-methylation433.66784.896267.270600.063530.000298.1420.000
  Overall510.417101.655311.172709.661530.000190.526156.570