Leonard You Sunwoo MD, Presenter: Nothing to Disclose

Seung Hong Choi MD, PhD, Abstract Co-Author: Nothing to Disclose

Tae Jin Yoon, Abstract Co-Author: Nothing to Disclose

Ji-Hoon Kim MD, Abstract Co-Author: Nothing to Disclose

Chul-Ho Sohn MD, Abstract Co-Author: Nothing to Disclose

Kee Hyun Chang MD, PhD, Abstract Co-Author: Nothing to Disclose

Moon Hee Han MD, Abstract Co-Author: Nothing to Disclose

In patients with glioblastoma multiforme (GBM), epigenetic silencing of O6-methylguanine DNA methyltransferase (MGMT), a DNA repair enzyme, is one of the most important prognostic and predictive biomarkers associated with better outcomes as well as susceptibility to temozolomide therapy. The aim of the present study is to retrospectively determine whether the apparent diffusion coefficient (ADC) values measured by diffusion MR imaging are correlated with MGMT promoter methylation quantitatively analyzed by immunohistochemistry in patients with GBM.

The study was approved by the institutional review board and was HIPAA compliant. Newly diagnosed GBM patients (n=30) were enrolled. All participants underwent standard b-value (b=0, 1000 s/mm2) diffusion MR imaging within 2 weeks before surgery. All GBMs were analyzed by using an ADC histogram approach based on enhancing solid portion. The methylation status of MGMT promoter was quantitatively measured by using methylation-specific multiplex ligation probe amplification (MS-MLPA) from cryopreserved tumor specimen. In addition, Ki-67 ratio, p53 and EGFR gene amplification were also quantitatively analyzed in each tumor. In all GBMs, the ADC values were correlated with quantitative MGMT promoter methylation status, Ki-67 ratio, and p53 and EGFR amplification using a linear regression model.

The range of MGMT promoter methylation status was from 0 to 0.92 (mean, 0.222). The mean ADC value showed a negative relationship with Ki-67 ratio (R2=0.281, P=0.035), whereas p53 and EGFR gene amplification status was not statistically related. The mean ADC values of the enhancing tumor portion revealed a positive relationship with MGMT promoter methylation status (R2=0.256, P<0.05).

In GBMs, we found that ADC values were significantly correlated with Ki-67 ratio as well as MGMT promoter methylation status.

We believe that ADC values may merit further development as a noninvasive biomarker potentially useful in predicting sensitivity and emerging resistance to temozolomide treatment.

Sunwoo, L, Choi, S, Yoon, T, Kim, J, Sohn, C, Chang, K, Han, M, Correlation of Apparent Diffusion Coefficient Values Measured by Diffusion MR Imaging and MGMT Promoter Methylation Quantitatively Analyzed by Using MS-MLPA in Patients with Glioblastoma Multiforme.  Radiological Society of North America 2011 Scientific Assembly and Annual Meeting, November 26 - December 2, 2011 ,Chicago IL. http://archive.rsna.org/2011/11008493.html