Stem cell marker CD133 affects clinical outcome in glioma patients.
OBJECTIVE
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.


METHODS
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.
Zeppernick
Felix
F
Division of Neurosurgical Research, Department of Neurosurgery, University of Heidelberg, Germany.
Ahmadi
Rezvan
R
Campos
Benito
B
Dictus
Christine
C
Helmke
Burkhard M
BM
Becker
Natalia
N
Lichter
Peter
P
Unterberg
Andreas
A
Radlwimmer
Bernhard
B
Herold-Mende
Christel C
CC
D000071916:AC133 Antigen; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis*; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010455:Peptides; D011379:Prognosis; D013234:Stem Cells / Q000378:metabolism*; D016019:Survival Analysis
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides