Relevance of combinatorial profiles of intermediate filaments and transcription factors for glioma histogenesis

Abstract

In order to define specific markers for histogenesis of three well-characterized subgroups of human gliomas (pilocytic astrocytomas, glioblastoma multiforme and oligodendrogliomas), we studied the expression of relevant markers that characterize gliomagenesis, by immunohistochemistry and in situ hybridization. They include the intermediate filament proteins glial fibrillary acidic protein (GFAP), vimentin and nestin, the transcription factors Olig2, Nkx2.2 and Sox10, and the proteolipid protein transcripts plp/dm20. We show that the three major categories of human gliomas express a combinatorial profile of markers that gives new insights to their histogenesis and may help diagnosis. Pilocytic astrocytomas strongly express GFAP, vimentin, Olig2, Nkx2.2 and Sox10 but not nestin. In contrast, glioblastomas strongly express GFAP, vimentin and nestin but these tumours are heterogeneous regarding the expression of the transcription factors studied. Finally, in oligodendrogliomas, intermediate filament proteins are generally not observed whereas Olig2 was found in almost all tumour cells nuclei while only a subpopulation of tumour cells expressed Nkx2.2 and Sox10.

The Role of Sox Transcription Factors in Brain Tumourigenesis

“…Consistently with several other studies we have reported that Sox10 is expressed in both paediatric and adult gliomas and ependymomas with a higher expression in low grade tumours compared to high grade tumours (Addo-Yobo, et al, 2006;Bannykh, et al, 2006;Colin, et al, 2007;Ferletta, et al, 2007). On the contrary Schlierf et al found that when investigating the mRNA levels of Sox10 in glioma the expression levels were lower compared to adult brain (Schlierf, et al, 2007).…”

“…Some researchers have tried to subgroup well-characterized gliomas depending on their expression of GFAP, vimentin, Olig2, Nkx2.2, Sox10 and nestin. They suggest that gliomas with strong expression of GFAP, vimentin, Olig2, Nkx2.2 and Sox10 can be identified as pilocytic astrocytomas, further robust expression of GFAP, vimentin and nestin can categorize GBM and oligodendrogliomas can be recognized by Olig2 expression in almost all tumour cells while Sox10 and Nkx2.2 was found in subpopulations of tumour cells, these findings are not definite but may to some degree extend the diagnostic possibilities (Colin, et al, 2007). Moreover the study indicate how heterogeneous the gliomas are and emphasize the difficulties in finding treatment that will target all different tumour cells from the bulk cells to the tumor-initiating cells.…”

“…The lack of Sox10 in medulloblastomas may be explained by the theory that gliomas and medulloblastomas probably originate from different tumour-initiating cells (Marino, et al, 2000). The expression of Sox10 by itself is not enough to characterize a subgroup of gliomas as pilocytic astrocytomas, but together with other markers it may be possible (Colin, et al, 2007;Rousseau, et al, 2006). Some researchers have tried to subgroup well-characterized gliomas depending on their expression of GFAP, vimentin, Olig2, Nkx2.2, Sox10 and nestin.…”

Nestin expression in brain tumors: its utility for pathological diagnosis and correlation with the prognosis of high-grade gliomas

“…Nestin is classified as a type VI intermediate filament protein [1]. During neural embryogenesis, nestin is expressed in neuroepithelial stem cells and is then downregulated in most mature central nervous system (CNS) cells [1].…”

Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma

“…To visualize human tumor cells in the rat brain and to determine their distribution outside the tumor core, we used a human-specific nestin staining, a protein expressed by the vast majority of GBM cells (15,22,23). Interestingly, treated tumors revealed a more homogeneous morphology compared with the controls (Fig.…”