Glioblastoma classification

Hierarchical molecular classification of IDH-wildtype glioblastomas revealed 3 distinct groups of IDH-wildtype glioblastomas. One major cluster was characterized by mutations in PDGFRA, amplification of CDK4 and PDGFRA, homozygous deletion of CDKN2A/B, and absence of TERTp mutations. This cluster was significantly associated with older age (P = .021), higher Ki-67 score (P = .007), poor prognosis (P = .012), and a periventricular tumor location 1).

Radiographic contact of glioblastoma (GBM) tumors with the lateral ventricle and adjacent stem cell niche correlates with poor patient prognosis, but the cellular basis of this difference is unclear. Bartkowiak et al. reveal and functionally characterize distinct immune microenvironments that predominate in subtypes of GBM distinguished by proximity to the lateral ventricle. Mass cytometry analysis of IDH-wildtype human tumors identified elevated T cell checkpoint receptor expression and greater abundance of a specific CD32+CD44+HLA-DRhigh macrophage population in ventricle-contacting GBM. Multiple computational analysis approaches, phospho-specific cytometry, and focal resection of GBMs confirmed and extended these findings. Phospho-flow quantified cytokine-induced immune cell signaling in ventricle-contacting GBM revealing differential signaling between GBM subtypes. Subregion analysis within a given tumor supported initial findings and revealed intratumoral compartmentalization of T cell memory and exhaustion phenotypes within GBM subtypes. Collectively, these results characterize immunotherapeutic targetable features of macrophages and suppressed lymphocytes in glioblastomas defined by MRI-detectable lateral ventricle contact 2).

For IDH status analysis, WHO recommends immunohistochemical (IHC) determination of IDH1-R132H, the most frequent mutated form. For IDH1 mutation-negative cases, if the patient is younger than 55 years, it is recommended to complete the study by sequencing both IDH1 and IDH2 genes. For patients≥ 55 years, only those with a history of a preexisting lower grade glioma, those with midline location (in which “Diffuse midline glioma H3 K27M-mutant” has not been discarded), and those with known ATRX mutation should be sequenced. The methylation status of the promoter of methylguanine methyl transferase (MGMT) gene has been largely recognized as a predictive factor for alkylating chemotherapy in GB 3)

Glioblastoma recurrence

Glioblastoma IDH Wildtype 9440/3

Giant cell glioblastoma 9441/3

Gliosarcoma 9442/3

Epithelioid glioblastoma 9440/3

Glioblastoma IDH Mutant 9440/3

Glioblastoma NOS.

Inoperable glioblastoma

The understanding of molecular subtypes of gliomas recently led to the World Health Organization Classification of Tumors of the Central Nervous System 2016 classification criteria for these tumors, introducing the concept of primary glioblastoma and secondary glioblastomas based on genetic alterations and gene or protein expression profiles.

With the advance of genomics research, there have been a new breakthrough in the molecular classification of gliomas. Glioblastoma (WHO grade Ⅳ) could be subtyped to proneural, neural, classical, and mesenchymal according to the mRNA expression. Low-grade gliomas (WHO grade Ⅱ and Ⅲ) could be divided into 5 types using 1p/19q co-deletion, isocitrate dehydrogenase(IDH) mutation, and TERTp (promotor region) mutation. In 2016, a new classification of tumors of the central nervous system was proposed, and some new markers such as IDH1 mutation were introduced into the diagnosis of gliomas. Genotype and phenotype were integrated to diagnose gliomas. In the meantime, precision treatment for gliomas has also been vigorously developed 4).

Glioblastoma multiforme in the motor area.

Butterfly glioblastoma

Cerebellar Glioblastoma Multiforme.

Elderly Glioblastoma.

Pediatric Glioblastoma.

The giant cell glioblastoma is a histological variant of glioblastoma, presenting a prevalence of bizarre, multinucleated (more than 20 nuclei) giant (up to 400 μm diameter) cells.

It is of great importance to seek further subclassifications, biomarkers, and new treatment modalities to make a significant change in survival for individuals 5).

MGMT-unmethylated glioblastoma.

Higa N, Akahane T, Yokoyama S, Yonezawa H, Uchida H, Takajo T, Kirishima M, Hamada T, Matsuo K, Fujio S, Hanada T, Hosoyama H, Yonenaga M, Sakamoto A, Hiraki T, Tanimoto A, Yoshimoto K. A tailored next-generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas. Cancer Sci. 2020 Oct;111(10):3902-3911. doi: 10.1111/cas.14597. Epub 2020 Sep 6. PMID: 32748499; PMCID: PMC7541004.
Bartkowiak T, Lima SM, Hayes MJ, Mistry AM, Brockman AA, Sinnaeve J, Leelatian N, Roe CE, Mobley BC, Chotai S, Weaver KD, Thompson RC, Chambless LB, Ihrie RA, Irish JM. An immunosuppressed microenvironment distinguishes lateral ventricle-contacting glioblastomas. JCI Insight. 2023 May 16:e160652. doi: 10.1172/jci.insight.160652. Epub ahead of print. PMID: 37192001.
Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10;352(10):997-1003. doi: 10.1056/NEJMoa043331. PMID: 15758010.
Hua W, Mao Y. [Advance of molecular subtyping and precise treatment for gliomas]. Zhonghua Wai Ke Za Zhi. 2017 Jan 1;55(1):63-66. doi: 10.3760/cma.j.issn.0529-5815.2017.01.016. Chinese. PubMed PMID: 28056258.
Fekete B, Werlenius K, Örndal C, Rydenhag B. Prognostic factors for glioblastoma patients - a clinical population-based study. Acta Neurol Scand. 2016 Jun;133(6):434-41. doi: 10.1111/ane.12481. Epub 2015 Sep 11. PubMed PMID: 26358197.
  • glioblastoma_classification.txt
  • Last modified: 2023/05/16 23:50
  • by administrador