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. 2008 Jan 28;7(2):755–764. doi: 10.1111/j.1750-3639.1997.tb01062.x

A Molecular Genetic Model of Astrocytoma Histopathology

David N Louis 1,✉
PMCID: PMC8098471  PMID: 9161727

Abstract

As the molecular events responsible for astrocytoma formation and progression are being clarified, it is becoming possible to correlate these alterations with the specific histopathological and biological features of astrocytoma, anaplastic astrocytoma and glioblastoma multiforme. In WHO grade II astrocytomas, autocrine stimulation by the platelet‐derived growth factor system coupled with inactiva‐tion of the p53 gene may lead to a growth stimulus in the face of decreased cell death with slow net growth ensuing. Such cells would also have defective responses to DNA damage and impaired DNA repair, setting the stage for future malignant change. Such biological scenarios recapitulate many of the clinicopathological features of WHO grade II astrocytomas. Anaplastic astrocytomas further display release of a critical cell cycle brake that involves the CDKN2/p16, RB and CDK4 genes. This results in mitoses seen histologically; clinically, there is more conspicuous, rapid growth. Finally, glioblastomas may emerge from the microenviron‐mental outgrowth of more malignant clones in a complex vicious cycle that involves necrosis, hypoxia, growth factor release, angiogenesis and clonal selection; growth signals mediated by activation of epidermal growth factor receptors may precipitate glioblastomas. It is clear as well that glioblastoma multiforme can arise via a number of independent genetic pathways, although the clinical significance of these distinctions remains unclear.

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