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Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas.
Acta Neuropathol 2010; 120(6):707-18AN

Abstract

WHO grading of human brain tumors extends beyond a strictly histological grading system by providing a basis predictive for the clinical behavior of the respective neoplasm. For example, patients with glioblastoma WHO grade IV usually show a less favorable clinical course and receive more aggressive first-line treatment than patients with anaplastic astrocytoma WHO grade III. Here we provide evidence that the IDH1 status is more prognostic for overall survival than standard histological criteria that differentiate high-grade astrocytomas. We sequenced the isocitrate dehydrogenase 1 gene (IDH1) at codon 132 in 382 patients with anaplastic astrocytoma and glioblastoma from the NOA-04 trial and from a prospective translational cohort study of the German Glioma Network. Patients with anaplastic astrocytomas carried IDH1 mutations in 60%, and patients with glioblastomas in 7.2%. IDH1 was the most prominent single prognostic factor (RR 2.7; 95% CI 1.6-4.5) followed by age, diagnosis and MGMT. The sequence from more favorable to poorer outcome was (1) anaplastic astrocytoma with IDH1 mutation, (2) glioblastoma with IDH1 mutation, (3) anaplastic astrocytoma without IDH1 mutation and (4) glioblastoma without IDH1 mutation (p < 0.0001). In this combined set of anaplastic astrocytomas and glioblastomas both, IDH1 mutation and IDH1 expression status were of greater prognostic relevance than histological diagnosis according to the current WHO classification system. Our data indicate that much of the prognostic significance of patient age is due to the predominant occurrence of IDH1 mutations in younger patients. Immunohistochemistry using a mutation-specific antibody recognizing the R132H mutation yielded similar results. We propose to complement the current WHO classification and grading of high-grade astrocytic gliomas by the IDH1 mutation status and to use this combined histological and molecular classification in future clinical trials.

Authors+Show Affiliations

Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21088844

Citation

Hartmann, Christian, et al. "Patients With IDH1 Wild Type Anaplastic Astrocytomas Exhibit Worse Prognosis Than IDH1-mutated Glioblastomas, and IDH1 Mutation Status Accounts for the Unfavorable Prognostic Effect of Higher Age: Implications for Classification of Gliomas." Acta Neuropathologica, vol. 120, no. 6, 2010, pp. 707-18.
Hartmann C, Hentschel B, Wick W, et al. Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. Acta Neuropathol. 2010;120(6):707-18.
Hartmann, C., Hentschel, B., Wick, W., Capper, D., Felsberg, J., Simon, M., ... von Deimling, A. (2010). Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. Acta Neuropathologica, 120(6), pp. 707-18. doi:10.1007/s00401-010-0781-z.
Hartmann C, et al. Patients With IDH1 Wild Type Anaplastic Astrocytomas Exhibit Worse Prognosis Than IDH1-mutated Glioblastomas, and IDH1 Mutation Status Accounts for the Unfavorable Prognostic Effect of Higher Age: Implications for Classification of Gliomas. Acta Neuropathol. 2010;120(6):707-18. PubMed PMID: 21088844.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. AU - Hartmann,Christian, AU - Hentschel,Bettina, AU - Wick,Wolfgang, AU - Capper,David, AU - Felsberg,Jörg, AU - Simon,Matthias, AU - Westphal,Manfred, AU - Schackert,Gabriele, AU - Meyermann,Richard, AU - Pietsch,Torsten, AU - Reifenberger,Guido, AU - Weller,Michael, AU - Loeffler,Markus, AU - von Deimling,Andreas, Y1 - 2010/11/19/ PY - 2010/09/17/received PY - 2010/11/05/accepted PY - 2010/11/04/revised PY - 2010/11/20/entrez PY - 2010/11/23/pubmed PY - 2011/11/9/medline SP - 707 EP - 18 JF - Acta neuropathologica JO - Acta Neuropathol. VL - 120 IS - 6 N2 - WHO grading of human brain tumors extends beyond a strictly histological grading system by providing a basis predictive for the clinical behavior of the respective neoplasm. For example, patients with glioblastoma WHO grade IV usually show a less favorable clinical course and receive more aggressive first-line treatment than patients with anaplastic astrocytoma WHO grade III. Here we provide evidence that the IDH1 status is more prognostic for overall survival than standard histological criteria that differentiate high-grade astrocytomas. We sequenced the isocitrate dehydrogenase 1 gene (IDH1) at codon 132 in 382 patients with anaplastic astrocytoma and glioblastoma from the NOA-04 trial and from a prospective translational cohort study of the German Glioma Network. Patients with anaplastic astrocytomas carried IDH1 mutations in 60%, and patients with glioblastomas in 7.2%. IDH1 was the most prominent single prognostic factor (RR 2.7; 95% CI 1.6-4.5) followed by age, diagnosis and MGMT. The sequence from more favorable to poorer outcome was (1) anaplastic astrocytoma with IDH1 mutation, (2) glioblastoma with IDH1 mutation, (3) anaplastic astrocytoma without IDH1 mutation and (4) glioblastoma without IDH1 mutation (p < 0.0001). In this combined set of anaplastic astrocytomas and glioblastomas both, IDH1 mutation and IDH1 expression status were of greater prognostic relevance than histological diagnosis according to the current WHO classification system. Our data indicate that much of the prognostic significance of patient age is due to the predominant occurrence of IDH1 mutations in younger patients. Immunohistochemistry using a mutation-specific antibody recognizing the R132H mutation yielded similar results. We propose to complement the current WHO classification and grading of high-grade astrocytic gliomas by the IDH1 mutation status and to use this combined histological and molecular classification in future clinical trials. SN - 1432-0533 UR - https://www.unboundmedicine.com/medline/citation/21088844/Patients_with_IDH1_wild_type_anaplastic_astrocytomas_exhibit_worse_prognosis_than_IDH1_mutated_glioblastomas_and_IDH1_mutation_status_accounts_for_the_unfavorable_prognostic_effect_of_higher_age:_implications_for_classification_of_gliomas_ L2 - https://dx.doi.org/10.1007/s00401-010-0781-z DB - PRIME DP - Unbound Medicine ER -