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Title:
IDH mutation status and role of WHO grade and mitotic index in overall survival in grade IIāIII diffuse gliomas | Acta Neuropathologica
Description:
Diffuse gliomas are up till now graded based upon morphology. Recent findings indicate that isocitrate dehydrogenase (IDH) mutation status defines biologically distinct groups of tumors. The role of tumor grade and mitotic index in patient outcome has not been evaluated following stratification by IDH mutation status. To address this, we interrogated 558 WHO grade IIāIII diffuse gliomas for IDH1/2 mutations and investigated the prognostic impact of WHO grade within IDH-mutant and IDH-wild type tumor subsets independently. The prognostic impact of grade was modest in IDH-mutant [hazard ratio (HR) = 1.21, 95 % confidence interval (CI) = 0.91ā1.61] compared to IDH-wild type tumors (HR = 1.74, 95 % CI = 0.95ā3.16). Using a dichotomized mitotic index cut-off of 4/1000 tumor cells, we found that while mitotic index was significantly associated with outcome in IDH-wild type tumors (log-rank p < 0.0001, HR = 4.41, 95 % CI = 2.55ā7.63), it was not associated with outcome in IDH-mutant tumors (log-rank p = 0.5157, HR = 1.10, 95 % CI = 0.80ā1.51), and could demonstrate a statistical interaction (p < 0.0001) between IDH mutation and mitotic index (i.e., suggesting that the effect of mitotic index on patient outcome is dependent on IDH mutation status). Patient age, an established prognostic factor in diffuse glioma, was significantly associated with outcome only in the IDH-wild type subset, and consistent with prior data, 1p/19q co-deletion conferred improved outcome in the IDH-mutant cohort. These findings suggest that stratification of grade IIāIII gliomas into subsets defined by the presence or absence of IDH mutation leads to subgroups with distinct prognostic characteristics. Further evaluation of grading criteria and prognostic markers is warranted within IDH-mutant versus IDH-wild type diffuse grade IIāIII gliomas as independent entities.
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Keywords {š}
pubmed, google, scholar, article, idh, cas, gliomas, cancer, central, van, grade, prognostic, mutations, mutation, glioma, clin, tumors, molecular, anaplastic, aldape, oncol, survival, lowgrade, center, mitotic, diffuse, outcome, wang, classification, university, status, deimling, pathol, doijco, friedman, usa, acta, index, tumor, patients, oligodendroglioma, dois, reifenberger, neuropathol, analysis, wesseling, astrocytomas, zhang, bent, material,
Topics {āļø}
month download article/chapter idh-wild type tumors elizabeth vera-bolanos idh-wild type subset grade iiāiii gliomas van den bent low-grade diffuse gliomas diffuse low-grade gliomas idh-mutant [hazard ratio bauke ylstraĀ &Ā pieter wesseling central nervous system health/national cancer institute idh wild-type intermediate-grade infiltrating astrocytomas proliferation markers ki-67/mib-1 hemispheric low-grade gliomas low-grade hemispheric gliomas secondary high-grade gliomas supratentorial low-grade glioma cerebral low-grade glioma neuropathology-haarlem consensus guidelines van den berg van essen hf phase iii trial grade ii astrocytomas full article pdf grade ii gliomas ontario cancer institute related subjects mgmt promoter status idh mutation status academic medical center human glioblastoma multiforme newly diagnosed glioblastoma den dunnen wf privacy choices/manage cookies idh-mutant tumors idh-mutant cohort van der valk human anaplastic astrocytomas quantitative microsatellite analysis integrated genomic analysis lower-grade gliomas low-grade astrocytomas idh1 mutant glioblastoma low-grade gliomas lower-grade glioma single-center experience idh mutation leads idh mutation identifies
Questions {ā}
- Hartmann C, Hentschel B, Tatagiba M, Schramm J, Schnell O, Seidel C, Stein R, Reifenberger G, Pietsch T, von Deimling A, Loeffler M, Weller M (2011) Molecular markers in low-grade gliomas: predictive or prognostic?
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headline:IDH mutation status and role of WHO grade and mitotic index in overall survival in grade IIāIII diffuse gliomas
description:Diffuse gliomas are up till now graded based upon morphology. Recent findings indicate that isocitrate dehydrogenase (IDH) mutation status defines biologically distinct groups of tumors. The role of tumor grade and mitotic index in patient outcome has not been evaluated following stratification by IDH mutation status. To address this, we interrogated 558 WHO grade IIāIII diffuse gliomas for IDH1/2 mutations and investigated the prognostic impact of WHO grade within IDH-mutant and IDH-wild type tumor subsets independently. The prognostic impact of grade was modest in IDH-mutant [hazard ratio (HR)Ā =Ā 1.21, 95Ā % confidence interval (CI)Ā =Ā 0.91ā1.61] compared to IDH-wild type tumors (HRĀ =Ā 1.74, 95Ā % CIĀ =Ā 0.95ā3.16). Using a dichotomized mitotic index cut-off of 4/1000 tumor cells, we found that while mitotic index was significantly associated with outcome in IDH-wild type tumors (log-rank pĀ <Ā 0.0001, HRĀ =Ā 4.41, 95Ā % CIĀ =Ā 2.55ā7.63), it was not associated with outcome in IDH-mutant tumors (log-rank pĀ =Ā 0.5157, HRĀ =Ā 1.10, 95Ā % CIĀ =Ā 0.80ā1.51), and could demonstrate a statistical interaction (pĀ <Ā 0.0001) between IDH mutation and mitotic index (i.e., suggesting that the effect of mitotic index on patient outcome is dependent on IDH mutation status). Patient age, an established prognostic factor in diffuse glioma, was significantly associated with outcome only in the IDH-wild type subset, and consistent with prior data, 1p/19q co-deletion conferred improved outcome in the IDH-mutant cohort. These findings suggest that stratification of grade IIāIII gliomas into subsets defined by the presence or absence of IDH mutation leads to subgroups with distinct prognostic characteristics. Further evaluation of grading criteria and prognostic markers is warranted within IDH-mutant versus IDH-wild type diffuse grade IIāIII gliomas as independent entities.
datePublished:2015-02-21T00:00:00Z
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IDH
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headline:IDH mutation status and role of WHO grade and mitotic index in overall survival in grade IIāIII diffuse gliomas
description:Diffuse gliomas are up till now graded based upon morphology. Recent findings indicate that isocitrate dehydrogenase (IDH) mutation status defines biologically distinct groups of tumors. The role of tumor grade and mitotic index in patient outcome has not been evaluated following stratification by IDH mutation status. To address this, we interrogated 558 WHO grade IIāIII diffuse gliomas for IDH1/2 mutations and investigated the prognostic impact of WHO grade within IDH-mutant and IDH-wild type tumor subsets independently. The prognostic impact of grade was modest in IDH-mutant [hazard ratio (HR)Ā =Ā 1.21, 95Ā % confidence interval (CI)Ā =Ā 0.91ā1.61] compared to IDH-wild type tumors (HRĀ =Ā 1.74, 95Ā % CIĀ =Ā 0.95ā3.16). Using a dichotomized mitotic index cut-off of 4/1000 tumor cells, we found that while mitotic index was significantly associated with outcome in IDH-wild type tumors (log-rank pĀ <Ā 0.0001, HRĀ =Ā 4.41, 95Ā % CIĀ =Ā 2.55ā7.63), it was not associated with outcome in IDH-mutant tumors (log-rank pĀ =Ā 0.5157, HRĀ =Ā 1.10, 95Ā % CIĀ =Ā 0.80ā1.51), and could demonstrate a statistical interaction (pĀ <Ā 0.0001) between IDH mutation and mitotic index (i.e., suggesting that the effect of mitotic index on patient outcome is dependent on IDH mutation status). Patient age, an established prognostic factor in diffuse glioma, was significantly associated with outcome only in the IDH-wild type subset, and consistent with prior data, 1p/19q co-deletion conferred improved outcome in the IDH-mutant cohort. These findings suggest that stratification of grade IIāIII gliomas into subsets defined by the presence or absence of IDH mutation leads to subgroups with distinct prognostic characteristics. Further evaluation of grading criteria and prognostic markers is warranted within IDH-mutant versus IDH-wild type diffuse grade IIāIII gliomas as independent entities.
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Diffuse glioma
IDH
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name:Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
name:The University of Texas Health Science Center, Houston, USA
name:Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
name:Department of Neurosurgery, Massachusetts General Hospital, Boston, USA
name:Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
name:Horizon Health, Lewisville, USA
name:Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA
name:Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands
name:Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
name:Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
name:Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
name:Department of Pathology, G1.3510, The University of Texas MD Anderson Cancer Center, Houston, USA
name:Princess Margaret Cancer Centre and Ontario Cancer Institute, Toronto, Canada
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