TY - JOUR
T1 - IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival
T2 - a grading problem for WHO
AU - Reuss, David E.
AU - Mamatjan, Yasin
AU - Schrimpf, Daniel
AU - Capper, David
AU - Hovestadt, Volker
AU - Kratz, Annekathrin
AU - Sahm, Felix
AU - Koelsche, Christian
AU - Korshunov, Andrey
AU - Olar, Adriana
AU - Hartmann, Christian
AU - Reijneveld, Jaap C.
AU - Wesseling, Pieter
AU - Unterberg, Andreas
AU - Platten, Michael
AU - Wick, Wolfgang
AU - Herold-Mende, Christel
AU - Aldape, Kenneth
AU - von Deimling, Andreas
N1 - Publisher Copyright:
© 2015, Springer-Verlag Berlin Heidelberg.
PY - 2015/6/26
Y1 - 2015/6/26
N2 - The WHO 2007 classification of tumors of the CNS distinguishes between diffuse astrocytoma WHO grade II (A IIWHO2007) and anaplastic astrocytoma WHO grade III (AA IIIWHO2007). Patients with A IIWHO2007 are significantly younger and survive significantly longer than those with AA IIIWHO2007. So far, classification and grading relies on morphological grounds only and does not yet take into account IDH status, a molecular marker of prognostic relevance. We here demonstrate that WHO 2007 grading performs poorly in predicting prognosis when applied to astrocytoma carrying IDH mutations. Three independent series including a total of 1360 adult diffuse astrocytic gliomas with IDH mutation containing 683 A IIIDHmut, 562 AA IIIIDHmut and 115 GBMIDHmut have been examined for age distribution and survival. In all three series patients with A IIIDHmut and AA IIIIDHmut were of identical age at presentation of disease (36–37 years) and the difference in survival between grades was much less (10.9 years for A IIIDHmut, 9.3 years for AA IIIIDHmut) than that reported for A IIWHO2007versus AA IIIWHO2007. Our analyses imply that the differences in age and survival between A IIWHO2007 and AA IIIWHO2007 predominantly depend on the fraction of IDH-non-mutant astrocytomas in the cohort. This data poses a substantial challenge for the current practice of astrocytoma grading and risk stratification and is likely to have far-reaching consequences on the management of patients with IDH-mutant astrocytoma.
AB - The WHO 2007 classification of tumors of the CNS distinguishes between diffuse astrocytoma WHO grade II (A IIWHO2007) and anaplastic astrocytoma WHO grade III (AA IIIWHO2007). Patients with A IIWHO2007 are significantly younger and survive significantly longer than those with AA IIIWHO2007. So far, classification and grading relies on morphological grounds only and does not yet take into account IDH status, a molecular marker of prognostic relevance. We here demonstrate that WHO 2007 grading performs poorly in predicting prognosis when applied to astrocytoma carrying IDH mutations. Three independent series including a total of 1360 adult diffuse astrocytic gliomas with IDH mutation containing 683 A IIIDHmut, 562 AA IIIIDHmut and 115 GBMIDHmut have been examined for age distribution and survival. In all three series patients with A IIIDHmut and AA IIIIDHmut were of identical age at presentation of disease (36–37 years) and the difference in survival between grades was much less (10.9 years for A IIIDHmut, 9.3 years for AA IIIIDHmut) than that reported for A IIWHO2007versus AA IIIWHO2007. Our analyses imply that the differences in age and survival between A IIWHO2007 and AA IIIWHO2007 predominantly depend on the fraction of IDH-non-mutant astrocytomas in the cohort. This data poses a substantial challenge for the current practice of astrocytoma grading and risk stratification and is likely to have far-reaching consequences on the management of patients with IDH-mutant astrocytoma.
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U2 - 10.1007/s00401-015-1438-8
DO - 10.1007/s00401-015-1438-8
M3 - Article
C2 - 25962792
AN - SCOPUS:84929709037
SN - 0001-6322
VL - 129
SP - 867
EP - 873
JO - Acta neuropathologica
JF - Acta neuropathologica
IS - 6
M1 - 1438
ER -