411O - A pilot study correlating IDH-1/2 gene status with 2-hydroxyglutarate (2HG) concentration in plasma and urine from patients (pts) with glioma

Date 01 October 2012
Event ESMO Congress 2012
Session CNS tumors
Topics Central Nervous System Malignancies
Translational Research
Presenter Giuseppe Lombardi
Authors G. Lombardi1, G. Corona2, P. Farina3, F. Zustovich3, R. Bertorelle4, P. Fiduccia3, A. Della Puppa5, M.P. Gardiman6, A. Salvalaggio3, G. Toffoli2, V. Zagonel7
  • 1U.o.oncologia Medica, Istituto Oncologico Veneto-IRCCS, 35128 - Padova/IT
  • 2Molecular Oncology And Translational Medicine, Experimental and Clinical Pharmacology Unit, Aviano/IT
  • 3Oncologia Medica 1, Istituto Oncologico Veneto-IRCCS, 35128 - Padova/IT
  • 4Molecular Immunology And Oncology, Istituto Oncologico Veneto-IRCCS, 35128 - Padova/IT
  • 5Neurosurgery Department, Azienda Ospedaliera di Padova, Padova/IT
  • 6Pathology, Azienda Ospedaliera di Padova, 35128 - Padova/IT
  • 7Department Of Oncology, IOV-IRCCS, 35138 - Padova/IT

Abstract

Background

IDH-1/2 mutations are a prognostic markers in gliomas. These mutations results in the production of 2HG. We investigated whether 2HG produced by IDH-1/2 mutant gliomas accumulates in patient's plasma and urine and whether this accumulation can be used to assess IDH-1/2 mutation status.

Methods

we prospectively studied PTS with intracranial gliomas and measurable disease on brain-MRI. All PTS had a partial surgical resection or a recurrent disease. The resected tissues were analyzed for IDH-1/2 mutational status; subsequently, in absence of chemotherapy and after 3 weeks from a prior surgery, a plasma and an overnight-urine samples collection were taken from consecutive PTS. 2HG concentrations were determinate by liquid chromatography tandem mass spectrometry. The statistical significance of the difference in the level of 2HG between the PTS with IDH-1/2 mutated and control group were evaluated by non parametric Mann- Whitney test.

Results

we analyzed 13 PTS with IDH-1 mutated and 13 PTS with IDH-1/2 wild-type; 2 PTS with low-grade glioma and 24 PTS with high-grade glioma; 10 females and 16 males. In all PTS we analyzed the mean 2HG concentration in plasma (P_2HG) and urine samples normalized by creatinine concentration (U_2HG). The results are shown in Table 1. We found significant differences in mean U_2HG, and in mean P_2HG/U_2HG in patients with or without IDH mutated. No statistically significant associations of tumor volume and U_2HG, of tumor volume and P_2HG were found in all PTS and in PTS with IDH1 mutated.

Conclusions

U_2HG and P_2HG/U_2HG might be used as markers to differentiate between gliomas with and without IDH mutated. No associations were found between tumor volume and U_2HG and P_2HG, indicating that 2HG might not be utilized as marker to monitor tumor growth. However, a larger number of samples need to be analyzed to draw final conclusions.

IDH wt IDH mutated p
U_2HG* 7.49 ± 3.87 5.00 ± 3.08 0.03
P_2HG (ng/mL) 86.42 ± 38.74 112.74 ± 73.19 0.26
P_2HG/U_2HG* 13.96 ± 7.54 23.83 ± 9.00 0.006

*Concentration of 2HG (µg/mL) normalized by creatinine concentration (mg/mL)

Disclosure

All authors have declared no conflicts of interest.