IJCEP Copyright © 2007-All rights reserved.
Int J Clin Exp Pathol 2013;6(3):334-348

Review Article
What is the clinical value of cancer stem cell markers in gliomas?

Rikke Hedegaard Dahlrot, Simon Kjær Hermansen, Steinbjørn Hansen, Bjarne Winther Kristensen

Department of Oncology, Odense University Hospital, Odense, Denmark; Department of Pathology, Odense University Hospital, Odense,
Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark

Received December 4, 2012; Accepted December 19, 2012; Epub February 15, 2013; Published March 1, 2013

Abstract: 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. (IJCEP1212006).

Keywords: Glioma, prognosis, cancer stem cell, immunohistochemistry, CD133, nestin

Address correspondence to: Dr. Bjarne W Kristensen, Department of Pathology, Odense University Hospital, Winsløwparken 15, 5000
Odense C, Denmark. E-mail: bjarne.winther.kristensen@ouh.regionsyddanmark.dk