Correlation of apparent diffusion coefficient values measured by diffusion MRI and MGMT promoter methylation semiquantitatively analyzed with MS-MLPA in patients with glioblastoma multiforme
Article first published online: 28 SEP 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Magnetic Resonance Imaging
Volume 37, Issue 2, pages 351–358, February 2013
How to Cite
Sunwoo, L., Choi, S. H., Park, C.-K., Kim, J. W., Yi, K. S., Lee, W. J., Yoon, T. J., Song, S. W., Kim, J. E., Kim, J. Y., Kim, T. M., Lee, S.-H., Kim, J.-H., Sohn, C.-H., Park, S.-H., Kim, I. H. and Chang, K.-H. (2013), Correlation of apparent diffusion coefficient values measured by diffusion MRI and MGMT promoter methylation semiquantitatively analyzed with MS-MLPA in patients with glioblastoma multiforme. J. Magn. Reson. Imaging, 37: 351–358. doi: 10.1002/jmri.23838
- Issue published online: 24 JAN 2013
- Article first published online: 28 SEP 2012
- Manuscript Accepted: 24 AUG 2012
- Manuscript Received: 15 FEB 2012
- National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea. Grant Number: 1120300
- Korea Healthcare Technology R&D Projects, Ministry for Health, Welfare & Family Affairs. Grant Number: A112028
- apparent diffusion coefficient (ADC);
- O6-methylguanine DNA methyltransferase (MGMT);
- methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA);
- methylation ratio;
To retrospectively determine whether the apparent diffusion coefficient (ADC) values correlate with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation semiquantitatively analyzed by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in patients with glioblastoma.
Materials and Methods:
The study was approved by the Institutional Review Board and was Health Insurance Portability and Accountability Act (HIPAA) compliant. Newly diagnosed patients with glioblastoma (n = 26) were analyzed with an ADC histogram approach based on enhancing solid portion. The methylation status of MGMT promoter was assessed by methylation-specific polymerase chain reaction (MSP) and by MS-MLPA. MS-MLPA is a semiquantitative method that determines the methylation ratio. The Ki-67 labeling index was also analyzed. The mean and 5th percentile ADC values were correlated with MGMT promoter methylation status and Ki-67 labeling index using a linear regression model. Progression-free survival (PFS) was also correlated with the ADC values using Kaplan–Meier survival analysis.
The mean methylation ratio was 0.21 ± 0.20. By MSP, there were 5 methylated and 21 unmethylated tumors. The mean ADC revealed a positive relationship with MGMT promoter methylation ratio (P = 0.015) and was also significantly different according to MSP-determined methylation status (P = 0.011). Median PFS was significantly related with methylation ratio (P = 0.017) and MSP-derived methylation status (P = 0.025). A positive relationship was demonstrated between PFS and the mean ADC value (P = 0.001). The 5th percentile ADC values showed a significant negative relationship with Ki-67 labeling index (P = 0.036).
We found that ADC values were significantly correlated with PFS as well as with MGMT promoter methylation status. We believe that ADC values may merit further investigation as a noninvasive biomarker for predicting treatment response. J. Magn. Reson. Imaging 2013;37:351–358. © 2012 Wiley Periodicals, Inc.