<p>(A–C) GFAP immunohistochemistry of astrocytes in the normal brain (A, A′), WHO II low-grade glioma (B, B′) and glioblastoma (GBM; C, C′, C″) at 1× (A, B, C) and 40× (A′, B′, C′, C″). Note that tumor-associated astrocytes (TAAs) are morphologically different than normal astrocytes. Moreover, in low grade glioma, TAAs are present within and surrounding the tumor and all of these astrocytes have a ‘reactive’ morphology identified by swollen cell bodies as well as multipolar and hyperextended processes (B′). Within GBM (C), astrocytes are present in two areas: the peri-tumoral area, where the astrocytes have a ‘reactive’ morphology (C′) similar to low grade astrocytes and the perivascular niche, where the astrocytes still have swollen cell bodies but have a more uni-polar or bi-polar morphology (C″). Scale bars: A, B, C = 300 µm, A′, B′, C′, C″ = 15 µm. D) Unbiased hierarchical clustering of astrocytes from normal brain, low-grade glioma and GBM indicates that, when factoring in the mRNA expression levels of approximately 15,000 genes significantly expressed on the array, TAAs are very different from normal astrocytes, however most genes are similarly regulated between low grade-associated and GBM-associated astrocytes and thus, low grade-associated and GBM-associated astrocytes do not segregate.</p
