Phosphorous Magnetic Resonance Spectroscopy and Molecular Markers in IDH1 Wild Type Glioblastoma

SIMPLE SUMMARY: Gliobastoma is one of the deadliest tumors overall, yet the most common malignant brain tumor. The new World Health Organization Classification of Brain Tumors brought changes in how we look at this type of malignancy. Now we know that glioblastoma is rather a spectrum of similar tumors, but with some distinct characteristics that include molecular footprint, response to therapy and with that overall survival, among others. We hypothesised that by employing phosphorous magnetic resonance we will be able to show differences in cellular energy metabolism in these various subtypes of glioblastoma. For example, we found indices of faster cell reproduction and tumor growth in MGMT-methylated and EGFR-amplified tumors. These tumors also could have reduced energetic state or tissue oxygenation due to the increased necrosis. Tumors with EGFR-amplification could have increased apoptotic activity regardless of their MGMT status. Our study indicated various differences in energetic metabolism in tumors with different molecular characteristics, which could potentially be important in future therapeutic strategies. ABSTRACT: The World Health Organisation’s (WHO) classification of brain tumors requires consideration of both histological appearance and molecular characteristics. Possible differences in brain energy metabolism could be important in designing future therapeutic strategies. Forty-three patients with primary, isocitrate dehydrogenase 1 (IDH1) wild type glioblastomas (GBMs) were included in this study. Pre-operative standard MRI was obtained with additional phosphorous magnetic resonance spectroscopy (31-P-MRS) imaging. Following microsurgical resection of the tumors, biopsy specimens underwent neuropathological diagnostics including standard molecular diagnosis. The spectroscopy results were correlated with epidermal growth factor (EGFR) and [Formula: see text]-Methylguanine-DNA methyltransferase (MGMT) status. EGFR amplified tumors had significantly lower phosphocreatine (PCr) to adenosine triphosphate (ATP)-PCr/ATP and PCr to inorganic phosphate (Pi)-PCr/Pi ratios, and higher Pi/ATP and phosphomonoesters (PME) to phosphodiesters (PDE)-PME/PDE ratio than those without the amplification. Patients with MGMT-methylated tumors had significantly higher cerebral magnesium (Mg) values and PME/PDE ratio, while their PCr/ATP and PCr/Pi ratios were lower than in patients without the methylation. In survival analysis, not-EGFR-amplified, MGMT-methylated GBMs showed the longest survival. This group had lower PCr/Pi ratio when compared to MGMT-methylated, EGFR-amplified group. PCr/Pi ratio was lower also when compared to the MGMT-unmethylated, EGFR not-amplified group, while PCr/ATP ratio was lower than all other examined groups. Differences in energy metabolism in various molecular subtypes of wild-type-GBMs could be important information in future precision medicine approach.