IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas
Autor: | Kenneth Aldape, Erik P. Sulman, Lindsey Heathcock, Daniel P. Cahill, Hinke F. van Thuijl, Jaap C. Reijneveld, Ying Yuan, Terri S. Armstrong, Elizabeth Vera-Bolanos, Adriana Olar, Khalida Wani, Pieter Wesseling, Kristin Alfaro-Munoz, Mark R. Gilbert, Bauke Ylstra |
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Přispěvatelé: | Pathology, Neurology, CCA - Disease profiling |
Rok vydání: | 2015 |
Předmět: |
Oncology
IDH Adult Male medicine.medical_specialty Pathology Mitotic index IDH1 Adolescent Clinical Neurology pHH3 Biology Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] Article Pathology and Forensic Medicine Diffuse Glioma Cellular and Molecular Neuroscience Young Adult Internal medicine medicine 1p/19q Mitotic Index Humans Grading (tumors) Outcome Aged Retrospective Studies Brain Neoplasms Hazard ratio Glioma Middle Aged Survival Analysis Confidence interval Isocitrate Dehydrogenase Isocitrate dehydrogenase Chromosomes Human Pair 1 Diffuse glioma Cohort Mutation Female Neurology (clinical) Chromosome Deletion WHO grade |
Zdroj: | Acta Neuropathologica, 129, 585-96 Acta Neuropathologica, 129(4), 585. Springer Verlag Acta Neuropathologica, 129(4), 585-596. Springer Verlag Olar, A, Wani, K M, Alfaro-Munoz, K D, Heathcock, L E, van Thuijl, H F, Gilbert, M R, Armstrong, T S, Sulman, E P, Cahill, D P, Vera-Bolanos, E, Yuan, Y, Reijneveld, J C, Ylstra, B, Wesseling, P & Aldape, K D 2015, ' IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas ', Acta Neuropathologica, vol. 129, no. 4, pp. 585-596 . https://doi.org/10.1007/s00401-015-1398-z Acta Neuropathologica, 129, 4, pp. 585-96 |
ISSN: | 0001-6322 |
Popis: | Contains fulltext : 153032.pdf (Publisher’s version ) (Closed access) 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 II-III 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) = 0.91-1.61] compared to IDH-wild type tumors (HR = 1.74, 95 % CI = 0.95-3.16). 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 = 2.55-7.63), it was not associated with outcome in IDH-mutant tumors (log-rank p = 0.5157, HR = 1.10, 95 % CI = 0.80-1.51), 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 II-III 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 II-III gliomas as independent entities. |
Databáze: | OpenAIRE |
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