Pathology and Biology; Molecular Markers

Chapter 5 - Treatment Strategies for Anaplastic Astrocytoma and Glioblastoma

Low-grade gliomas (LGGs) are infiltrative diseases of the central nervous system (CNS), with cells found throughout the brain. The majority of tumour cells are found within 1–2 cm around the visible tumour on magnetic resonance imaging (MRI).

LGGs diffusely infiltrate the brain parenchyma and cannot be cured by surgery alone. The extent of tumour infiltration may be shown by isocitrate dehydrogenase (IDH) immunostaining: large dots = 10%–15% tumour cells, small dots = less than 10% tumour cell fraction.

Until 2016, the World Health Organization (WHO) classification of LGGs was based on histopathological features, and divided them into astrocytoma, oligodendroglioma and oligoastrocytoma. The 2016 WHO classification integrates for the first time histological and molecular features for glioma subtyping.

The 2016 WHO classification of CNS tumours is based both on histological and molecular features.
It separates LGGs into 3 categories:

  • Diffuse astrocytoma with mutation of the IDH Gene 1 or 2 (IDH1 or 2)
  • Astrocytoma IDH wildtype (wt)
  • Oligodendroglioma IDH mutant (IDHmt), and codeleted for chromosomal arms 1p and 19q (1p/19q codeleted)


Or, in the absence of genetic information, astrocytoma or oligodendroglioma not otherwise specified (NOS)<\strong>.<\p>

Mutations of IDH1 or 2 are gain of function mutations and result in the formation of a CpG island methylator Phenotype (CIMP). This results in the silencing of numerous genes, including tumour suppressors.

1p/19q codeletion results from an unbalanced whole- arm translocation between Chromosomes 1 and 19 with loss of the derivative chromosome t(1p:19q). IDHmt and 1p/19q codeleted tumours are usually associated with TERT Promoter mutations.

IDHwt LGGs are associated with intact alpha thalassaemia/ mental retardation syndrome X-linked gene (ATRX) expression. This gene, like p53, is involved in telomere maintenance.

Revision Questions

  1. What are the histological subtypes of LGGs?
  2. Which are the two most relevant molecular markers of LGGs?
  3. What is the typical molecular profile of an oligodendroglioma?

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Last update: 18 September 2017