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Stem Cell Marker CD133 Affects Clinical Outcome in Glioma Patients

Authors' Affiliations: ¹ Division of Neurosurgical Research, Department of Neurosurgery, and ² Institute of Pathology, University of Heidelberg; ³ Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany

Requests for reprints: Christel C. Herold-Mende, Sektion Neurochirurgische Forschung, Neurochirurgische Universitätsklinik, INF 400, 69120 Heidelberg, Germany. Phone: 49-6221-566405; Fax: 49-6221-565362; E-mail: H.Mende{at}med.uni-heidelberg.de.

Purpose: The CD133 antigen has been identified as a putative stem cell marker in normal and malignant brain tissues. In gliomas, it is used to enrich a subpopulation of highly tumorigenic cancer cells. According to the cancer stem cell hypothesis, CD133-positive cells determine long-term tumor growth and, therefore, are suspected to influence clinical outcome. To date, a correlation between CD133 expression in primary tumor tissues and patients' prognosis has not been reported.

Experimental Design: To address this question, we analyzed the expression of the CD133 stem cell antigen in a series of 95 gliomas of various grade and histology by immunohistochemistry on cryostat sections. Staining data were correlated with patient outcome.

Results: By multivariate survival analysis, we found that both the proportion of CD133-positive cells and their topological organization in clusters were significant (P < 0.001) prognostic factors for adverse progression-free survival and overall survival independent of tumor grade, extent of resection, or patient age. Furthermore, proportion of CD133-positive cells was an independent risk factor for tumor regrowth and time to malignant progression in WHO grade 2 and 3 tumors.

Conclusions: These findings constitute the first conclusive evidence that CD133 stem cell antigen expression correlates with patient survival in gliomas, lending support to the current cancer stem cell hypothesis.