Liya Wang MD, Presenter: Nothing to Disclose

Juliya Kalinina, Abstract Co-Author: Nothing to Disclose

Shaoxiong Wu PhD, Abstract Co-Author: Nothing to Disclose

Chad Ashley Holder MD, Abstract Co-Author: Nothing to Disclose

Erwin G. Van Meir, Abstract Co-Author: Nothing to Disclose

Hui Mao PhD, Abstract Co-Author: Nothing to Disclose

Mutation in the isocitrate dehydrogenase (IDH) is a common feature of a major subset of primary low grade gliomas. The IDH mutation specific metabolite 2-hydroxyglutarate (2HG) can be detected and quantified by magnetic resonance spectroscopy (MRS). This study investigates whether the 2HG concentration, a possible marker for IDH mutant activity, is related to tumor progressions.

2HG in 28 gliomas carrying IDH1/2 mutations were detected and quantified using 2D correlation MRS. Tumor volumes were determined from routine clinical MRI exams performed on each patient based on the enhancing portion of mass in post-contrast T1weighted imaging. Tumor grade and Ki-67 proliferation index (MIB) data were obtained from histopathology analysis. Two-tailed Spearman (P<0.05) was used for analyzing the correlation of 2HG concentration with tumor volumes (n=17) and MIB (n=18). Two-year follow-up MRI and 2HG levels determined using the tissue samples obtained from repeated biopsy from 4 patients were analyzed and compared.

Higher 2HG concentrations were found in tumors with higher grades. Higher 2HG level appears associated with the increased tumor volume and MIB index. However, 2HG levels in Grade IV tumor, which is considered as the secondary glioblastom multifprme (GBM) and different from low grade gliomas, is lower than those of Grade III gliomas. In all four cases with follow-up MRI and repeated biopsy, 2HG concentrations were increased when tumor progression took place from grade II to grade III two years later. In all four cases, routine MRI exams showed increased tumor volume and more pronounced contrast enhancing effect in tumors after two years. In comparison, 2HG levels obtained from MRS showed more than 2-fold of increase. These results provided patient specific examples demonstrating that the 2HG level is increasing with the elevated tumor grade in low grade gliomas carrying IDH mutations.

Findings of this study provide the evidence that IDH mutation specific 2HG level has a strong correlation with several clinically important prognostic measurements, such as tumor size and MIB index value. Excess 2HG accumulated in tumors may contribute to formation and malignant progression of glioma.

Association of increased 2HG level and tumor progression features suggests 2HG as a MRS detectable marker for predicting glioma prognosis.

Wang, L, Kalinina, J, Wu, S, Holder, C, Van Meir, E, Mao, H, 2-hydroxyglutarate (2HG) Level Is Associated to Tumor Progression in Gliomas Carrying IDH Mutations.  Radiological Society of North America 2013 Scientific Assembly and Annual Meeting, December 1 - December 6, 2013 ,Chicago IL. http://archive.rsna.org/2013/13016549.html