title: 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: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Leonard
authors.initials: L
authors.lastname: Sunwoo
authors.forename: Seung Hong
authors.initials: SH
authors.lastname: Choi
authors.forename: Chul-Kee
authors.initials: CK
authors.lastname: Park
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Kim
authors.forename: Kyung Sik
authors.initials: KS
authors.lastname: Yi
authors.forename: Woong Jae
authors.initials: WJ
authors.lastname: Lee
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Yoon
authors.forename: Sang Woo
authors.initials: SW
authors.lastname: Song
authors.forename: Ja Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Ji-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Sohn
authors.forename: Sung-Hye
authors.initials: SH
authors.lastname: Park
authors.forename: Il Han
authors.initials: IH
authors.lastname: Kim
authors.forename: Kee-Hyun
authors.initials: KH
authors.lastname: Chang
mesh_terms: D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes