Article,
IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas
(2015)
Abstract
// Heather E. Leeper 1 , Alissa A. Caron 2 , Paul A. Decker 3 , Robert B. Jenkins 5 , Daniel H. Lachance 4 , Caterina Giannini 5 1 Neuro-Oncology, Advocate Medical Group, Park Ridge, IL 60068, USA 2 Experimental Pathology, Mayo Clinic SW, Rochester, MN 55905, USA 3 Biomedical Statistics and Informatics, Mayo Clinic SW, Rochester, MN 55905, USA 4 Neurology, Mayo Clinic SW, Rochester, MN 55905, USA 5 Anatomic Pathology, Mayo Clinic SW, Rochester, MN 55905, USA Correspondence to: Caterina Giannini, e-mail: giannini.caterina@mayo.edu Keywords: diffuse gliomas, WHO grade II, IDH mutation, ATRX, 1p19q codeletion Received: March 12, 2015      Accepted: June 22, 2015      Published: July 03, 2015 ABSTRACT Background: Epigenetic, genetic, and molecular studies have identified several diagnostic and prognostic markers in diffuse gliomas. Their importance for evaluating WHO grade II gliomas has yet to be specifically delineated. Methods: We analyzed markers, including IDH mutation(IDHmut), 1p19q codeletion(1p19qcodel), ATRX expression loss(ATRX loss) and p53 overexpression, and outcomes in 159 patients with WHO grade II oligodendroglioma, oligoastrocytoma, and astrocytoma (2003–2012). Results: IDHmut was found in 141(91%) and ATRX loss in 64(87%) of IDHmut-noncodel tumors ( p = 0.003). All codeleted tumors ( n = 66) were IDHmut. Four subgroups were identified: IDHmut-codel, 66(43%); IDHmut-noncodel-ATRX loss, 60(39%); IDHmut-noncodel-ATRXwt, 9(6%); IDHwt, 14(9%). Median survival among 4 groups was significantly different ( p = 0.038), particularly in IDHmut-codel (median survival 15.6 years) compared to the remaining 3 groups ( p = 0.025). Survival by histology was not significant. Overall (OS), but not progression-free (PFS), survival was significantly longer with gross total resection vs. biopsy only ( p = 0.042). Outcomes for patients with subtotal resection were not significantly different from those with biopsy only. Among these uniformly treated patients, OS far exceeds PFS, particularly in those with 1p/19q codeletion. Conclusions: For WHO grade II diffuse glioma, molecular classification using 1p/19qcodel, IDHmut, and ATRX loss more accurately predicts outcome and should be incorporated in the neuropathologic evaluation.
