ATRX status correlates with 11C-methionine uptake in WHO grade II and III gliomas with IDH1 mutations.

Abstract

Recent studies on gliomas have shown frequent alterations in the alpha-thalassemia/mental retardation syndrome X-linked gene (ATRX). This study was designed to determine whether ATRX status correlates with uptake of 11C-methionine in WHO grades II and III gliomas. Sixty-two patients underwent 11C-methionine positron emission tomography scans prior to histological diagnosis. The tumor-to-normal ratio (T/N) of 11C-methionine uptake was calculated by dividing the maximum standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain. After surgery, tumor samples were subjected to immunohistochemistry for ATRX and IDH1-R132H followed by IDH1/2 sequencing. Twenty-seven of the sixty-two patients were found to have the IDH mutation. Nine of the twenty-seven gliomas harboring IDH mutations exhibited loss of nuclear ATRX expression, which is accompanied with an astrocytic tumor lineage and a poor prognosis. The mean T/N ratio in tumors with loss of nuclear ATRX expression was 2.20 ± 0.53, i.e., significantly lower than that of tumors with ATRX retention (3.28 ± 1.32, p = 0.0171, U test). Our study showed ATRX status to correlate with the T/N ratio and the outcomes of WHO grade II and III glioma patients with the IDH1 mutation. Our data provide new information on the biology and imaging characteristics of gliomas.