MGMT promoter methylation in glioblastoma

Santosh, Vani; Sravya, Palavalasa

doi:10.4103/0028-3886.236995

Cited by 5 publications

(10 citation statements)

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“…9 In the light of the ISNO consensus, the standard approach to all diffuse astrocytic and oligodendroglial gliomas begins with performing IHC for ATRX and IDH1 - R132H expression. 10 In the current study, we used immunohistochemistry to reveal IDH1 - R132H and ATRX status instead of sequencing, aiming to dispense a mature and straightforward tool for clinical practice. So, our results also revealed that the IDH1-R132H and (or) ATRX loss status could be necessary to provide the basic molecular information for the “integrated diagnosis” of gliomas.…”

Section: Discussionmentioning

confidence: 99%

Study of Surrogate Immunohistochemical Markers IDH1, ATRX, BRAF V600E, and p53 Mutation in Astrocytic and Oligodendroglial Tumors

Sharma

Mathur

Mittal

et al. 2022

Indian Journal of Neurosurgery

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Introduction In consonance with current the World Health Organization (WHO) classification of the central nervous system (CNS) tumors (2016), histological diagnosis of gliomas should be reinforced by molecular information. This study was performed to determine the frequency of isocitrate dehydrogenase 1 (IDH1), α thalassemia/intellectual disability syndrome X-linked (ATRX), p53, and BRAF V600E mutations in different grade astrocytomas and oligodendrogliomas. Methods Seventy-seven cases of astrocytoma and oligodendroglioma (7 pilocytic astrocytomas, 15 diffuse astrocytomas [DA], 4 anaplastic astrocytomas [AA], 29 glioblastomas [GBM], and 22 oligodendrogliomas) were analyzed using immunohistochemistry for IDH1 mutant protein, ATRX, p53, and BRAF as well as their clinicopathological features assessed. Results All pilocytic astrocytoma and primary glioblastoma cases were negative for an IDH1 mutation. IDH1 mutation was detected in 66.7% (10/15) of DA, 50% (2/4) of AA, 20.7% (6/29) of glioblastomas, and 81.8% (18/22) of oligodendroglioma cases. Loss of nuclear ATRX expression was found in 86.7% (13/15), 75% (3/4), and 34.5% (10/29) of DA, AA, and GBM cases, respectively. All oligodendroglioma cases showed retained ATRX expression. Both markers were found statistically significant in the above tumors (p <0.05). BRAF V600E mutation was detected in a single case of pilocytic astrocytoma and pleomorphic xanthoastrocytoma as well as both cases of epithelioid glioblastoma. Conclusions IDH1 and ATRX mutations are very common in diffuse astrocytoma and anaplastic astrocytoma, while they are rare in pilocytic astrocytoma and glioblastoma. Immunohistochemistry for IDH1 and ATRX can successfully characterize the diffuse gliomas into molecularly defined groups in the majority of the cases. BRAF V600E mutation is rare in astrocytic tumors in the Indian population.

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Section: Discussionmentioning

confidence: 99%

Study of Surrogate Immunohistochemical Markers IDH1, ATRX, BRAF V600E, and p53 Mutation in Astrocytic and Oligodendroglial Tumors

Sharma

Mathur

Mittal

et al. 2022

Indian Journal of Neurosurgery

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“…Majority of these mutations are IDH1 type, commonest being IDH1R132H . 13 IHC for IDH1R132H is a surrogate for the mutation, and DNA sequencing is advocated only for the rare IDH1/2 mutations whenever diffuse gliomas are immunonegative for IDH1R132H . 6…”

Section: Discussionmentioning

confidence: 99%

Clinical, Morphological, and Molecular Study of Diffuse WHO Grade II and III Astrocytomas: A Retrospective Analysis from a Single Tertiary Care Institute

Veduruvada

Uppin

Konatam

et al. 2021

Indian J Med Paediatr Oncol

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Introduction Astrocytomas are the most common gliomas, classified on the basis of grade and IDH mutation status according to the World Health Organization (WHO) 2016 update. IDH mutations are seen in 70 to 80% of diffuse grade II and III astrocytomas and are associated with better outcome. They serve as predictive biomarker in IDH-targeted therapies such as small-molecule inhibitors or vaccines. Objective The aim of this study was to analyze the clinical, morphological, immunohistochemical, and molecular genetic characteristics of diffuse astrocytoma (DA: grades II and III). The IDH mutant and wild-type tumors are compared and contrasted with survival analysis on follow-up. Materials and Methods This was a retrospective study conducted on surgically resected tumor specimens. The hematoxylin and eosin-stained slides were examined for histologic features. Immunohistochemistry (IHC) was performed using IDH1R132H, ATRX, p53, and Ki67. All cases of negative immunohistochemical expression of IDH1R132H were subjected to IDH1 mutation analysis by Sanger sequencing. Overall survival was estimated by the Kaplan-Meier method using the log-rank (Mantel–Cox) test. Results The study included 51 cases of DA in the age of 17 to 66 years, mean ± standard deviation was 35.5 ± 9.7 years, and male:female ratio was 2:1.The IDH1R132H cytoplasmic immunopositivity was seen in 36 cases (70.5%), of which 63.6% were of grade II and 72.5% were of grade III. ATRX showed loss of expression in 50 cases (98%), and p53 showed diffuse strong immunohistochemical expression in all the cases of IDH mutant tumors. The difference in the age at presentation for IDH mutant (32.5 years) and wild type tumors (38 years) was statistically significant. Median survival was 55.3 months and 22.2 months in of IDH mutant and wild type cases, respectively. Conclusion IHC and sequencing for IDH mutations is helpful in making an integrated diagnosis and classifying definite molecular subgroups of astrocytic tumors. Mutations in IDH core-elate with survival. IDH mutant tumors showed longer survival duration and are good prognostic indicators.

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“…The EGFR gene codes for a cell surface tyrosine kinase receptor that initiates the PI3K and MAPK pathways, which contribute to cell survival and proliferation. The most common EGFR gene 34 aberration encountered in glioblastoma is its amplification. A proportion of the EGFR amplified tumors carry the EGFR vIII mutation, which plays a significant role in gliomagenesis, increasing the survival of the mutant cells as well as adjacent cells through paracrine activity.…”

Section: Epidermal Growth Factor Receptor (Egfr) Gene Mutationmentioning

confidence: 99%

“…33 WHO grade II, III and IV diffuse gliomas typically have a proliferation index of less than 5%, 5-10% and 15-20%, respectively. 34 supplemented by molecular characterization of the lesion to generate an integrated diagnosis (Fig. 3).…”

Section: Proliferative Indexmentioning

confidence: 99%

A radical shift in the diagnostic approach to diffuse gliomas

Panth

2020

J Pathol Nep

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Astrocytic tumours comprise the majority of central nervous system tumours and they have been traditionally graded as recommended by World Health Organization on the basis of atypia, mitoses, microvascular proliferation and necrosis. The 2016 WHO classification of diffuse gliomas incorporates both molecular and histological criteria to categorize these tumours to better predict behavior. A layered diagnostic format is now the recommended approach with the WHO grade being assigned on histological criteria to be supplemented by molecular characterization once the result of isocitrate dehydrogenase is available. The presence of 1p/19q-codeletion has now been included in the definition of oligodendrogliomas. Oligoastrocytomas have now almost vanished as an entity because they are classified as either astrocytomas or oligodendrogliomas after molecular testing. Tests have to be modified in resource limited settings to reach a molecular diagnosis based on new scientific literature and research.

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MGMT promoter methylation in glioblastoma

Cited by 5 publications

References 0 publications

Study of Surrogate Immunohistochemical Markers IDH1, ATRX, BRAF V600E, and p53 Mutation in Astrocytic and Oligodendroglial Tumors

Study of Surrogate Immunohistochemical Markers IDH1, ATRX, BRAF V600E, and p53 Mutation in Astrocytic and Oligodendroglial Tumors

Clinical, Morphological, and Molecular Study of Diffuse WHO Grade II and III Astrocytomas: A Retrospective Analysis from a Single Tertiary Care Institute

A radical shift in the diagnostic approach to diffuse gliomas

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