TY - JOUR
T1 - IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas
AU - Leeper, Heather E.
AU - Caron, Alissa A.
AU - Decker, Paul A.
AU - Jenkins, Robert B.
AU - Lachance, Daniel H.
AU - Giannini, Caterina
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - 1p19q codeletion
KW - ATRX
KW - Diffuse gliomas
KW - IDH mutation
KW - WHO grade II
UR - http://www.scopus.com/inward/record.url?scp=84945162385&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84945162385&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.4497
DO - 10.18632/oncotarget.4497
M3 - Article
C2 - 26210286
AN - SCOPUS:84945162385
SN - 1949-2553
VL - 6
SP - 30295
EP - 30305
JO - Oncotarget
JF - Oncotarget
IS - 30
ER -