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Role of Amide Proton Transfer Weighted MRI in Predicting MGMTp Methylation Status, p53-Status, Ki-67 Index, IDH-Status, and ATRX Expression in WHO Grade 4 High Grade Glioma

Durmo, Faris LU orcid ; Lätt, Jimmy LU ; Rydelius, Anna LU ; Englund, Elisabet LU orcid ; Salomonsson, Tim LU orcid ; Liebig, Patrick ; Bengzon, Johan LU ; van Zijl, Peter C M ; Knutsson, Linda LU orcid and Sundgren, Pia C LU orcid (2025) In Tomography 11(6).
Abstract


Objectives: To assess amide proton transfer weighted (APTw) MR imaging capabilities in differentiating high-grade glial tumors across alpha-thalassemia/mental retardation X-linked (ATRX) expression, tumor-suppressor protein p53 expression (p53), O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation, isocitrate dehydrogenase (IDH) status, and proliferation marker Ki-67 (Ki-67 index) as a preoperative diagnostic aid.
Material & Methods: A total of 42 high-grade glioma WHO grade 4 (HGG) patients were evaluated prospectively (30 males and 12 females). All patients were examined using conventional MRI, including the following: T1w-MPRAGE pre- and post-contrast administration, conventional T2w and 3D FLAIR, and... (More)


Objectives: To assess amide proton transfer weighted (APTw) MR imaging capabilities in differentiating high-grade glial tumors across alpha-thalassemia/mental retardation X-linked (ATRX) expression, tumor-suppressor protein p53 expression (p53), O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation, isocitrate dehydrogenase (IDH) status, and proliferation marker Ki-67 (Ki-67 index) as a preoperative diagnostic aid.
Material & Methods: A total of 42 high-grade glioma WHO grade 4 (HGG) patients were evaluated prospectively (30 males and 12 females). All patients were examined using conventional MRI, including the following: T1w-MPRAGE pre- and post-contrast administration, conventional T2w and 3D FLAIR, and APTw imaging with a 3T MR scanner. Receiver operating characteristic (ROC) curves were calculated for the APTw% mean, median, and max signal for the different molecular biomarkers. A logistic regression model was constructed for combined mean and median APTw% signals for p53 expression.
Results: The whole-tumor max APTw% signal could significantly differentiate MGMTp from non-MGMTp HGG,
p = 0.035. A cutoff of 4.28% max APTw% signal yielded AUC (area under the curve) = 0.702, with 70.6% sensitivity and 66.7% specificity. The mean/median APTw% signals differed significantly in p53 normal versus p53-overexpressed HGG s: 1.81%/1.83% vs. 1.15%/1.18%,
p = 0.002/0.006, respectively. Cutoffs of 1.25%/1.33% for the mean/median APTw% signals yielded AUCs of 0.786/0.757, sensitivities of 76.9%/76.9%, and specificities of 50%/66.2%,
p = 0.002/0.006, respectively. A logistic regression model with a combined mean and median APTw% signal for p53 status yielded an AUC = 0.788 and 76.9% sensitivity and 66.2% specificity. ATRX-, IDH- wild type (wt) vs. mutation (mut), and the level of Ki-67 did not differ significantly, but trends were found: IDH-wt and low Ki-67 showed higher mean/median/max APTw% signals vs. IDH-mut and high Ki-67, respectively. ATRX-wt vs. mutation showed higher mean and median APTw% signals but lower max APTw% signal.
Conclusions: APTw imaging can potentially be a useful marker for the stratification of p53 expression and MGMT status in high-grade glioma in the preoperative setting and potentially aid surgical decision-making.

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author
; ; ; ; ; ; ; ; and
organization
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type
Contribution to journal
publication status
published
subject
keywords
Humans, Male, Female, Glioma/genetics, Adult, Middle Aged, Magnetic Resonance Imaging/methods, Tumor Suppressor Protein p53/metabolism, X-linked Nuclear Protein, Ki-67 Antigen/metabolism, Brain Neoplasms/genetics, Isocitrate Dehydrogenase/genetics, Tumor Suppressor Proteins/genetics, DNA Modification Methylases/genetics, Prospective Studies, DNA Repair Enzymes/genetics, Aged, Biomarkers, Tumor/metabolism, DNA Methylation, Neoplasm Grading, Young Adult, Adolescent, ROC Curve
in
Tomography
volume
11
issue
6
article number
64
publisher
MDPI AG
external identifiers
  • scopus:105009315150
  • pmid:40560010
ISSN
2379-1381
DOI
10.3390/tomography11060064
language
English
LU publication?
yes
id
8fc77722-d8f7-4a28-a5ec-90844a382dec
date added to LUP
2025-07-10 18:32:18
date last changed
2025-07-12 03:14:13
@article{8fc77722-d8f7-4a28-a5ec-90844a382dec,
  abstract     = {{<p><br>
 Objectives: To assess amide proton transfer weighted (APTw) MR imaging capabilities in differentiating high-grade glial tumors across alpha-thalassemia/mental retardation X-linked (ATRX) expression, tumor-suppressor protein p53 expression (p53), O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation, isocitrate dehydrogenase (IDH) status, and proliferation marker Ki-67 (Ki-67 index) as a preoperative diagnostic aid. <br>
 Material &amp; Methods: A total of 42 high-grade glioma WHO grade 4 (HGG) patients were evaluated prospectively (30 males and 12 females). All patients were examined using conventional MRI, including the following: T1w-MPRAGE pre- and post-contrast administration, conventional T2w and 3D FLAIR, and APTw imaging with a 3T MR scanner. Receiver operating characteristic (ROC) curves were calculated for the APTw% mean, median, and max signal for the different molecular biomarkers. A logistic regression model was constructed for combined mean and median APTw% signals for p53 expression.<br>
 Results: The whole-tumor max APTw% signal could significantly differentiate MGMTp from non-MGMTp HGG, <br>
 p = 0.035. A cutoff of 4.28% max APTw% signal yielded AUC (area under the curve) = 0.702, with 70.6% sensitivity and 66.7% specificity. The mean/median APTw% signals differed significantly in p53 normal versus p53-overexpressed HGG s: 1.81%/1.83% vs. 1.15%/1.18%, <br>
 p = 0.002/0.006, respectively. Cutoffs of 1.25%/1.33% for the mean/median APTw% signals yielded AUCs of 0.786/0.757, sensitivities of 76.9%/76.9%, and specificities of 50%/66.2%, <br>
 p = 0.002/0.006, respectively. A logistic regression model with a combined mean and median APTw% signal for p53 status yielded an AUC = 0.788 and 76.9% sensitivity and 66.2% specificity. ATRX-, IDH- wild type (wt) vs. mutation (mut), and the level of Ki-67 did not differ significantly, but trends were found: IDH-wt and low Ki-67 showed higher mean/median/max APTw% signals vs. IDH-mut and high Ki-67, respectively. ATRX-wt vs. mutation showed higher mean and median APTw% signals but lower max APTw% signal. <br>
 Conclusions: APTw imaging can potentially be a useful marker for the stratification of p53 expression and MGMT status in high-grade glioma in the preoperative setting and potentially aid surgical decision-making.<br>
 </p>}},
  author       = {{Durmo, Faris and Lätt, Jimmy and Rydelius, Anna and Englund, Elisabet and Salomonsson, Tim and Liebig, Patrick and Bengzon, Johan and van Zijl, Peter C M and Knutsson, Linda and Sundgren, Pia C}},
  issn         = {{2379-1381}},
  keywords     = {{Humans; Male; Female; Glioma/genetics; Adult; Middle Aged; Magnetic Resonance Imaging/methods; Tumor Suppressor Protein p53/metabolism; X-linked Nuclear Protein; Ki-67 Antigen/metabolism; Brain Neoplasms/genetics; Isocitrate Dehydrogenase/genetics; Tumor Suppressor Proteins/genetics; DNA Modification Methylases/genetics; Prospective Studies; DNA Repair Enzymes/genetics; Aged; Biomarkers, Tumor/metabolism; DNA Methylation; Neoplasm Grading; Young Adult; Adolescent; ROC Curve}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{6}},
  publisher    = {{MDPI AG}},
  series       = {{Tomography}},
  title        = {{Role of Amide Proton Transfer Weighted MRI in Predicting MGMTp Methylation Status, p53-Status, Ki-67 Index, IDH-Status, and ATRX Expression in WHO Grade 4 High Grade Glioma}},
  url          = {{http://dx.doi.org/10.3390/tomography11060064}},
  doi          = {{10.3390/tomography11060064}},
  volume       = {{11}},
  year         = {{2025}},
}