Abstract
BackgroundDespite of a multimodal approach, recurrences can hardly be prevented in glioblastoma. This may be in part due to so called glioma stem cells. However, there is no established marker to identify these stem cells.MethodsPaired samples from glioma patients were analyzed by immunohistochemistry for expression of the following stem cell markers: CD133, Musashi, Nanog, Nestin, octamer-binding transcription factor 4 (Oct4), and sex determining region Y-box 2 (Sox2). In addition, the expression of osteopontin (OPN) was investigated. The relative number of positively stained cells was determined. By means of Kaplan–Meier analysis, a possible association with overall survival by marker expression was investigated.ResultsSixty tissue samples from 30 patients (17 male, 13 female) were available for analysis. For Nestin, Musashi and OPN a significant increase was seen. There was also an increase (not significant) for CD133 and Oct4. Patients with mutated Isocitrate Dehydrogenase-1/2 (IDH-1/2) status had a reduced expression for CD133 and Nestin in their recurrent tumors. Significant correlations were seen for CD133 and Nanog between OPN in the primary and recurrent tumor and between CD133 and Nestin in recurrent tumors. By confocal imaging we could demonstrate a co-expression of CD133 and Nestin within recurrent glioma cells. Patients with high CD133 expression had a worse prognosis (22.6 vs 41.1 months, p = 0.013). A similar trend was seen for elevated Nestin levels (24.9 vs 41.1 months, p = 0.08).ConclusionsMost of the evaluated markers showed an increased expression in their recurrent tumor. CD133 and Nestin were associated with survival and are candidate markers for further clinical investigation.
Highlights
Despite of a multimodal approach, recurrences can hardly be prevented in glioblastoma
Most patients were diagnosed with World Health Organization (WHO) grade IV glioblastoma, one with grade II diffuse astrocytoma and one with grade III anaplastic astrocytoma
Co‐localization between Cluster of differentiation 133 (CD133) and Nestin After establishing simultaneous immunofluorescence staining for CD133 and Nestin we investigated if a colocalization of both markers could be detected within the same tumor cells
Summary
Despite of a multimodal approach, recurrences can hardly be prevented in glioblastoma. This may be in part due to so called glioma stem cells. The standard treatment approach with surgery followed by adjuvant radio-chemotherapy is not successful in eliminating all tumor cells permanently and has only a limited curative effect with a median overall survival less than 2 years [2,3,4]. Recurrence usually occurs within the multimodal treatment. One reason for treatment failure seems to be the presence of so-called cancer stem-like cells (CSCs), a subpopulation of tumor cells, which persist in the patient [5]. Like embryonal stem cells (ESCs), these highly malignant cells are characterized by perpetual self-renewal, proliferation and differentiation.
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