Recent data indicate that cancer stem cells (CSCs) are responsible for resistance of glioblastomas to radiotherapy and chemotherapy, thereby contributing to the poor survival of these patients. In order to identify novel prognostic markers in gliomas, several CSC markers have been investigated. This review summarizes current reports on putative glioma CSC markers and reviews the prognostic value of the individual immunohistochemical markers reported in the literature. Using the Pubmed database, twenty-seven CSC studies looking at membrane markers (CD133, podoplanin, CD15, and A2B5), filament markers (nestin), RNA-binding proteins (Musashi-1) and transcription factors (BMI1, SOX2, Id1 and Oct-4) qualified for this review. The level of CD133 and nestin increased with increasing malignancy grade, and for both markers a prognostic significance was identified in the majority of the studies. Moreover, the co-expression of CD133 and nestin was shown to have an even more powerful prognostic value than just single markers. Regarding podoplanin and Musashi-1, there was a trend towards a prognostic value when summarizing all studies. Especially the co-expression of Musashi-1 and MIB1 seemed promising. For the remaining markers CD15, A2B5, BMI1, SOX2, Id1 and Oct4, no prognostic value was found regarding overall survival in this review. In conclusion we find that CD133, nestin, CD133/nestin, podoplanin, Musashi-1 and Musashi-1/MIB1 are the most promising markers for future investigation. Evaluation in larger cohorts with known clinical data and known status of important biomarkers like MGMT and IDH1 is necessary to reveal their full clinical potential.
Keywords: CD133; Glioma; cancer stem cell; immunohistochemistry; nestin; prognosis.