title: IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO.
abstract: The WHO 2007 classification of tumors of the CNS distinguishes between diffuse astrocytoma WHO grade II (A II(WHO2007)) and anaplastic astrocytoma WHO grade III (AA III(WHO2007)). Patients with A II(WHO2007) are significantly younger and survive significantly longer than those with AA III(WHO2007). 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 II(IDHmut), 562 AA III(IDHmut) and 115 GBM(IDHmut) have been examined for age distribution and survival. In all three series patients with A II(IDHmut )and AA III(IDHmut) 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 II(IDHmut), 9.3 years for AA III(IDHmut)) than that reported for A II(WHO2007) versus AA III(WHO2007). Our analyses imply that the differences in age and survival between A II(WHO2007) and AA III(WHO2007) 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.
authors.affiliation: Department of Neuropathology, Institute of Pathology, University of Heidelberg, INF 224, 69120, Heidelberg, Germany.
authors.forename: David E
authors.initials: DE
authors.lastname: Reuss
authors.forename: Yasin
authors.initials: Y
authors.lastname: Mamatjan
authors.forename: Daniel
authors.initials: D
authors.lastname: Schrimpf
authors.forename: David
authors.initials: D
authors.lastname: Capper
authors.forename: Volker
authors.initials: V
authors.lastname: Hovestadt
authors.forename: Annekathrin
authors.initials: A
authors.lastname: Kratz
authors.forename: Felix
authors.initials: F
authors.lastname: Sahm
authors.forename: Christian
authors.initials: C
authors.lastname: Koelsche
authors.forename: Andrey
authors.initials: A
authors.lastname: Korshunov
authors.forename: Adriana
authors.initials: A
authors.lastname: Olar
authors.forename: Christian
authors.initials: C
authors.lastname: Hartmann
authors.forename: Jaap C
authors.initials: JC
authors.lastname: Reijneveld
authors.forename: Pieter
authors.initials: P
authors.lastname: Wesseling
authors.forename: Andreas
authors.initials: A
authors.lastname: Unterberg
authors.forename: Michael
authors.initials: M
authors.lastname: Platten
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.forename: Christel
authors.initials: C
authors.lastname: Herold-Mende
authors.forename: Kenneth
authors.initials: K
authors.lastname: Aldape
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D001254:Astrocytoma / Q000145:classification / Q000235:genetics* / Q000401:mortality*; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics* / Q000401:mortality*; D002878:Chromosomes, Human, Pair 1; D005260:Female; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016019:Survival Analysis; D014944:World Health Organization; D055815:Young Adult
chemical_list: D007521:Isocitrate Dehydrogenase