Glioblastoma multiforme classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]

Overview

Glioblastoma multiforme may be classified into several subtypes based on the origin (primary and secondary) and molecular alterations (classic, proneural, mesenchymal, and neural).

Classification

Based on the origin

Glioblastoma multiforme may be classified according to the origin into two subtypes: Primary and secondary.

Subtype of Glioblastoma multiforme	Characteristic features
Primary glioblastoma multiforme	De novo origin More aggressive Occurs in older patients
Secondary glioblastoma multiforme	Arises from pre-existing lower grade gliomas Less aggressive Occurs in younger patients

• Primary GBM is the most common form (about 95%) and arises typically de novo, within 3–6 months, in older patients.
• Secondary GBM arises from prior low-grade astrocytomas (over 10–15 years) in younger patients.
• Primary and secondary forms show some molecular differences.
• The end result of both sub type is same since the same pathways are affected and respond similarly to current standard treatment.
• Primary GBM often has amplified and mutated epidermal-growth factor receptor (EGFR) which encodes altered EGF receptor.
• Secondary GBM has increased signaling through PDGF-A receptor.
• Both types of mutations lead to increased tyrosine kinase receptor (TKR) activity and consequently to activation of RAS and PI3K pathways.
• Primary and secondary GBM may be indistinguishable histologically but apparently differ in genetic and epigenetic profiles.

Based on the molecular alterations

• the Cancer Genome Atlas (TCGA) divided GBM according to the molecular alterations into four subtypes:

1. Classic
2. Proneural
3. Mesenchymal
4. Neural

• Classical GBM is defined by aberrant EGFR amplification with astrocytic cell expression pattern and loss of chromosome 10.
• The mesenchymal subtype is defined by NF1 and PTEN mutations, a mesenchymal expression profile and less EGFR amplification than in other GBM types.
• The proneural subtype is characterized by PDGFRA focal amplification, TP53 and IDH1 mutations with an oligodenrocytic cell expression profile and younger presentation age.
• The neural subtype is characterized by normal brain tissue gene expression wuth astrocytic and oligodendrocytic cell markers.
• Most GBM tumors with IDH1 mutations have the proneural gene expression pattern but only 30% of preneural GBM has the IDH1 mutation.
• IDH1 mutation is a reliable and definitive molecular diagnostic criterion of secondary GBM compared to clinical criteria.
• The heterogeneity of GBM profiles leads to different treatment efficacy among patients.
• The therapy must be personalized to target each patient’s alterations in the molecular level.

References

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