The Oligodendroglial Lineage Marker OLIG2 Is Universally Expressed in Diffuse Gliomas

Abstract

Astrocytomas, oligodendrogliomas, and oligoastrocytomas, collectively referred to as diffuse gliomas, are the most common primary brain tumors. These tumors are classified by histologic similarity to differentiated astrocytes and oligodendrocytes, but this approach has major limitations in guiding modern treatment and research. Lineage markers represent a potentially useful adjunct to morphologic classification. The murine bHLH transcription factors Olig1 and Olig2 are expressed in neural progenitors and oligodendroglia and are essential for oligodendrocyte development. High OLIG expression alone has been proposed to distinguish oligodendrogliomas from astrocytomas, so we critically evaluated OLIG2 as a marker by immunohistochemical and oligonucleotide microarray analysis. OLIG2 protein is faithfully restricted to normal oligodendroglia and their progenitors in human brain. Immunohistochemical analysis of 180 primary, metastatic, and non-neural human tumors shows OLIG2 is highly expressed in all diffuse gliomas. Immunohistochemistry and microarray analyses demonstrate higher OLIG2 in anaplastic oligodendrogliomas versus glioblastomas, which are heterogeneous with respect to OLIG2 levels. OLIG2 protein expression is present but inconsistent and generally lower in most other brain tumors and is absent in non-neuroectodermal tumors. Overall, OLIG2 is a useful marker of diffuse gliomas as a class. However, expression heterogeneity of OLIG2 in astrocytomas precludes immunohistochemical classification of individual gliomas by OLIG2 alone.

Identification of OLIG2 as the most specific glioblastoma stem cell marker starting from comparative analysis of data from similar DNA chip microarray platforms

“…Second, exposure to glioma-relevant mitogens, such as EGF or PDGF, stimulates proliferation of Olig2+ rapidly dividing "type C" transit amplifying cells and glioma-like growths [72]. Moreover, all gliomas, irrespective of grade, express Olig2 in at least some fraction of the malignant cell population [42,[73][74][75][76][77][78]. Thus, our results seem consistent with the literature, in particular with the study of Ligon et al which showed that Olig2 is a marker of GSCs because Olig2 function is required for glioma formation in a genetically relevant murine model [42].…”

Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting

“…Olig2 is highly expressed in neural progenitors that give rise to oligodendrocytes and several subtypes of neurons (Lu et al, 2002). A number of studies have shown that Olig2 is widely expressed in astrocytomas and is required for tumor initiation and growth in vivo (Ligon et al, 2004;, suggesting a functional link between Olig2 expression and cancer stem cells in gliomas. Indeed, we found that Olig2 is differentially expressed in GSCs relative to the non-stem tumor cells isolated from almost all cases of GBM tumor specimens obtained in our group, which indicates that Olig2 is a common marker for GSC subpopulation (Bao et al, 2008;Li et al, 2009).…”

Diagnostic implications of IDH1-R132H and OLIG2 expression patterns in rare and challenging glioblastoma variants

“…Recent work has shown that although this oligodendroglial lineage marker, a bHLH transcription factor, is restricted to oligodendroglia and their progenitors in normal human brain, it is nearly universally expressed in diffuse human gliomas. 22 Thus, OLIG2 is not useful in the distinction of astrocytomas from oligodendrogliomas as was originally hoped, but can potentially help distinguish gliomas from other high-grade CNS and non-CNS malignancies, including sarcomas and primitive neuroectodermal tumors (PNET). 22 Additionally, OLIG2 is a particularly useful diagnostic marker for infiltrative tumors, such as gliomas because the protein has nuclear expression and as such, is often considerably easier to interpret than cytoplasmic markers such as glial fibrillary acidic protein (GFAP), which tends to produce background parenchymal staining.…”