ATRX status correlates with 11 C-methionine uptake in WHO grade II and III gliomas with IDH1 mutations
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.
KeywordsGlioma 11 C-methionine Positron emission tomography ATRX IDH
We thank Dr. Hiroaki Wakimoto (Harvard University, Boston) for invaluable advice. This work was supported by JSPS KAKENHI Grant Number 15K19954 (K. Tamura). Portions of this study were presented in abstract form at the 34th Annual Meeting of the Japan Society of Brain Tumor Pathology, Tokyo, Japan, May 27, 2016.
Compliance with ethical standards
Conflict of interest
The authors have no conflicts of interest to declare.
This study was approved by the Ethics Committee of the Tokyo Medical and Dental University. Informed consent was obtained from the patients and/or their guardians.
- 10.Reuss DE, Sahm F, Schrimpf D et al (2015) ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an “integrated” diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. Acta Neuropathol 129:133–146CrossRefPubMedGoogle Scholar
- 14.Louis DN, Ohgaki H, Wiestler OD et al (2007) World Health Organization histological classi cation of tumours of the central nervous system. International Agency for Research on Cancer, LyonGoogle Scholar
- 22.Marinoni I, Kurrer AS, Vassella E et al (2014) Loss of DAXX and ATRX are associated with chromosome instability and reduced survival of patients with pancreatic neuroendocrine tumors. Gastroenterology 146(453–460):e455Google Scholar