The prognostic role of IDH mutations in homogeneously treated patients with anaplastic astrocytomas and glioblastomas
Abstract The detection of IDH mutations in patients with diffusely infiltrating malignant astrocytomas resulted in substantial modifications in the concept of WHO classification of these tumors. An important underlying observation was that patients with anaplastic astrocytomas (AA) without IDH mutat...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2019-10-01
|
Series: | Acta Neuropathologica Communications |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s40478-019-0817-0 |
id |
doaj-8aea555c245049c2a3939159a8c99234 |
---|---|
record_format |
Article |
spelling |
doaj-8aea555c245049c2a3939159a8c992342020-11-25T03:50:45ZengBMCActa Neuropathologica Communications2051-59602019-10-017111110.1186/s40478-019-0817-0The prognostic role of IDH mutations in homogeneously treated patients with anaplastic astrocytomas and glioblastomasArne Christians0Antonia Adel-Horowski1Rouzbeh Banan2Ulrich Lehmann3Stephan Bartels4Felix Behling5Alonso Barrantes-Freer6Christine Stadelmann7Veit Rohde8Florian Stockhammer9Christian Hartmann10Department of Neuropathology, Institute of Pathology, Hannover Medical School (MHH)Department of Neurosurgery, University Medical Center GöttingenDepartment of Neuropathology, Institute of Pathology, Hannover Medical School (MHH)Institute of Pathology, Hannover Medical SchoolInstitute of Pathology, Hannover Medical SchoolDepartment of Neurosurgery, University Hospital TübingenInstitute of Neuropathology, University Medical Center GöttingenInstitute of Neuropathology, University Medical Center GöttingenDepartment of Neurosurgery, University Medical Center GöttingenDepartment of Neurosurgery, University Medical Center GöttingenDepartment of Neuropathology, Institute of Pathology, Hannover Medical School (MHH)Abstract The detection of IDH mutations in patients with diffusely infiltrating malignant astrocytomas resulted in substantial modifications in the concept of WHO classification of these tumors. An important underlying observation was that patients with anaplastic astrocytomas (AA) without IDH mutation had a clinical course similar to that of patients with glioblastomas (GBM). The underlying observations of the German Glioma Network and NOA-04, however, were based on mixed patient cohorts. While most GBM patients received combined radiochemotherapy, patients with AA usually had radiotherapy or chemotherapy only. This intrinsic shortcoming of the study raised the question of whether patients with AA, IDH wildtype, WHO grade III, might have better prognosis if treated with combined radiochemotherapy than patients with GBM receiving the same combination therapy. Thus, the question remains whether the established histopathological grading criteria for malignant astrocytomas in the absence of an IDH mutation are still important if neither vascular proliferation nor necrosis are detectable. All patients in the cohort investigated here with the diagnosis of AA or GBM were subjected to a combined radiochemotherapy according to the Stupp protocol independently of the histopathological diagnosis. Thus, the analysis of these patients allows to clarify whether patients with AA, IDH wildtype, WHO grade III have a prognosis similar to that of GBM, IDH wildtype, WHO grade IV, even under equivalent therapeutic conditions. We determined the IDH1 and IDH2 status by sequencing, the MGMT status by pyrosequencing after bisulfite treatment and the EGFR status of the patients by FISH. In fact, the patients with the histopathological diagnosis of an AA IDH wild-type under similar aggressive therapy showed a comparable and therefore no better prognosis (median overall survival (mOS) 16 months) than patients with a GBM (mOS 13 months). Instead, patients with an AA and an IDH mutation receiving the same therapy had a mOS of 54 months. Thus, it can be concluded that in the absence of an IDH mutation, the established histopathological grading criteria ‘necrosis’ and ‘vascular proliferation’ actually lose their prognostic significance. If, on the other hand, patients with malignant astrocytomas and an IDH mutation are examined, there is still a difference between patients with necrosis and/or vascular proliferation and those whose tumors do not show such characteristics. Accordingly, in patients with malignant astrocytomas with IDH mutation it can be concluded that a histological differentiation between AA IDH mutated and GBM IDH mutated remains beneficial from a prognostic perspective.http://link.springer.com/article/10.1186/s40478-019-0817-0IDH1IDH2MGMTEGFRPrognosisGrading |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Arne Christians Antonia Adel-Horowski Rouzbeh Banan Ulrich Lehmann Stephan Bartels Felix Behling Alonso Barrantes-Freer Christine Stadelmann Veit Rohde Florian Stockhammer Christian Hartmann |
spellingShingle |
Arne Christians Antonia Adel-Horowski Rouzbeh Banan Ulrich Lehmann Stephan Bartels Felix Behling Alonso Barrantes-Freer Christine Stadelmann Veit Rohde Florian Stockhammer Christian Hartmann The prognostic role of IDH mutations in homogeneously treated patients with anaplastic astrocytomas and glioblastomas Acta Neuropathologica Communications IDH1 IDH2 MGMT EGFR Prognosis Grading |
author_facet |
Arne Christians Antonia Adel-Horowski Rouzbeh Banan Ulrich Lehmann Stephan Bartels Felix Behling Alonso Barrantes-Freer Christine Stadelmann Veit Rohde Florian Stockhammer Christian Hartmann |
author_sort |
Arne Christians |
title |
The prognostic role of IDH mutations in homogeneously treated patients with anaplastic astrocytomas and glioblastomas |
title_short |
The prognostic role of IDH mutations in homogeneously treated patients with anaplastic astrocytomas and glioblastomas |
title_full |
The prognostic role of IDH mutations in homogeneously treated patients with anaplastic astrocytomas and glioblastomas |
title_fullStr |
The prognostic role of IDH mutations in homogeneously treated patients with anaplastic astrocytomas and glioblastomas |
title_full_unstemmed |
The prognostic role of IDH mutations in homogeneously treated patients with anaplastic astrocytomas and glioblastomas |
title_sort |
prognostic role of idh mutations in homogeneously treated patients with anaplastic astrocytomas and glioblastomas |
publisher |
BMC |
series |
Acta Neuropathologica Communications |
issn |
2051-5960 |
publishDate |
2019-10-01 |
description |
Abstract The detection of IDH mutations in patients with diffusely infiltrating malignant astrocytomas resulted in substantial modifications in the concept of WHO classification of these tumors. An important underlying observation was that patients with anaplastic astrocytomas (AA) without IDH mutation had a clinical course similar to that of patients with glioblastomas (GBM). The underlying observations of the German Glioma Network and NOA-04, however, were based on mixed patient cohorts. While most GBM patients received combined radiochemotherapy, patients with AA usually had radiotherapy or chemotherapy only. This intrinsic shortcoming of the study raised the question of whether patients with AA, IDH wildtype, WHO grade III, might have better prognosis if treated with combined radiochemotherapy than patients with GBM receiving the same combination therapy. Thus, the question remains whether the established histopathological grading criteria for malignant astrocytomas in the absence of an IDH mutation are still important if neither vascular proliferation nor necrosis are detectable. All patients in the cohort investigated here with the diagnosis of AA or GBM were subjected to a combined radiochemotherapy according to the Stupp protocol independently of the histopathological diagnosis. Thus, the analysis of these patients allows to clarify whether patients with AA, IDH wildtype, WHO grade III have a prognosis similar to that of GBM, IDH wildtype, WHO grade IV, even under equivalent therapeutic conditions. We determined the IDH1 and IDH2 status by sequencing, the MGMT status by pyrosequencing after bisulfite treatment and the EGFR status of the patients by FISH. In fact, the patients with the histopathological diagnosis of an AA IDH wild-type under similar aggressive therapy showed a comparable and therefore no better prognosis (median overall survival (mOS) 16 months) than patients with a GBM (mOS 13 months). Instead, patients with an AA and an IDH mutation receiving the same therapy had a mOS of 54 months. Thus, it can be concluded that in the absence of an IDH mutation, the established histopathological grading criteria ‘necrosis’ and ‘vascular proliferation’ actually lose their prognostic significance. If, on the other hand, patients with malignant astrocytomas and an IDH mutation are examined, there is still a difference between patients with necrosis and/or vascular proliferation and those whose tumors do not show such characteristics. Accordingly, in patients with malignant astrocytomas with IDH mutation it can be concluded that a histological differentiation between AA IDH mutated and GBM IDH mutated remains beneficial from a prognostic perspective. |
topic |
IDH1 IDH2 MGMT EGFR Prognosis Grading |
url |
http://link.springer.com/article/10.1186/s40478-019-0817-0 |
work_keys_str_mv |
AT arnechristians theprognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT antoniaadelhorowski theprognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT rouzbehbanan theprognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT ulrichlehmann theprognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT stephanbartels theprognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT felixbehling theprognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT alonsobarrantesfreer theprognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT christinestadelmann theprognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT veitrohde theprognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT florianstockhammer theprognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT christianhartmann theprognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT arnechristians prognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT antoniaadelhorowski prognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT rouzbehbanan prognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT ulrichlehmann prognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT stephanbartels prognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT felixbehling prognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT alonsobarrantesfreer prognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT christinestadelmann prognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT veitrohde prognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT florianstockhammer prognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas AT christianhartmann prognosticroleofidhmutationsinhomogeneouslytreatedpatientswithanaplasticastrocytomasandglioblastomas |
_version_ |
1724490796524109824 |