Correlation of apparent diffusion coefficient values measured by diffusion MRI and MGMT promoter methylation semiquantitatively analyzed with MS-MLPA in patients with glioblastoma multiforme

Abstract

Purpose: To retrospectively determine whether the apparent diffusion coefficient (ADC) values correlate with O(6)-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.

Results: 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).

Conclusion: 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.