Abstract
PurposeThe identification of prognostically and therapeutically relevant molecular markers is fundamental to the further development of personalised therapies in brain tumours. Current therapeutic options for the treatment of gliomas rely mainly on surgical resection and the inhibition of tumour cell proliferation by irradiation and chemotherapy. Glioma stem cells are a subpopulation of proliferating tumour cells that have self-renewal capacity and can give rise to heterogeneous cells that comprise the tumour and are thought to play a role in the resistance of gliomas to therapy. The aim of this study was to evaluate the expression of markers of glioma stem cells and differentiated glial cells in proliferating glioma cells in comparison to the overall expression of the respective markers in the tumour tissue.MethodsTissue microarrays were assembled from specimen of pilocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, oligodendroglioma, anaplastic oligodendroglioma, ependymoma, and anaplastic ependymoma. These were immunohistochemically double stained with antibodies against the proliferation-associated antigen Ki67 and marker proteins for glioma stem cells (CD133, Nestin, Musashi, CD15, CD44), and differentiated glioma cells (GFAP, MAP2c).ResultsThe expression of both glial and glioma stem cell markers differs between proliferating and non-proliferating glioma cells. Furthermore, the proliferating cells in the different glial tumour entities show a different expression profile.ConclusionFurther analysis of marker expression in proliferating glioma cells and correlation with clinical outcome and susceptibility to irradiation and chemotherapy might help establish new biomarkers and therapies for glioma.
Highlights
Along with metastases gliomas are the most prevalent tumours in the adult human brain
Considering the glioma stem cell hypothesis proposing a hierarchical organisation of tumour cells in glioma (Hale et al 2013; Singh et al 2004), we hypothesised that proliferating cells in glioma will show a different expression profile than non-proliferating tumour cells
To analyse marker expression in proliferating and non-proliferating tumour cells, specimen of pilocytic astrocytoma World Health Organization (WHO) grade I, diffuse astrocytoma WHO grade II, anaplastic astrocytoma WHO grade III, glioblastoma WHO grade IV, oligodendroglioma WHO grade II, anaplastic oligodendroglioma WHO grade III, ependymoma WHO grade II and anaplastic ependymoma WHO grade III were assembled to tissue microarrays (TMAs) to allow simultaneous processing of high sample numbers (Fig. 1a)
Summary
Along with metastases gliomas are the most prevalent tumours in the adult human brain. While some primary brain tumours like pilocytic astrocytoma, ependymoma, and ganglioglioma often follow a benign course, most glial tumours share a poor prognosis. This holds especially true for glioblastoma, the most prevalent and malignant primary. Molecular markers have been identified that are expressed by glioma stem cells For some of these marker proteins like CD133 and Musashi-1 a correlation between their expression and other prognostic factors could be shown (Dahlrot et al 2013; Pallini, 2008), but systematic studies analysing co-expression of different marker proteins on a single cell level have to the best of our knowledge not been performed
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