Prognostic significance of stem cell marker CD133 determined by promoter methylation but not by immunohistochemical expression in malignant gliomas.

Abstract

CD133 has played a pivotal role in the identification and isolation of brain tumor stem cells. The correlation between CD133 expression in tumor tissues with patients survival is still controversial. CD133 expression is determinated by methylation status of the promoter region 1–3. Aberrant methylation of CD133 was observed in glioblastoma. To date, a direct link between CD133 methylation and patient outcome has not been established.To address this question, we studied CD133 expression and promoter methylation in a series of 170 gliomas of various grade and histology, and investigated the correlation of CD133 expression and promoter methylation with patient outcome.We detected five CD133 promoter methylation patterns in 170 glioma samples: methylation only (M+, U−), unmethylation only (M−, U+), both methylation and unmethylation equally (M+, U+), high methylation and low unmethylation (M+, Ul), and low methylation and high unmethylation (Ml, U+). By multivariate survival analysis, we found CD133 promoter methylation status was significant (P < 0.01) prognostic factors for adverse progression-free survival and overall survival independent of tumor grade, extent of resection, or patient age. CD133 immunostaining showed considerable variability among tumors. While, there was lack of correlation between CD133 protein expression and patient’s survival. Furthermore, no correlation between CD133 protein expression and CD133 promoter methylation status was observed (Kw = −0.165).CD133 promoter methylation status in glioma is closely correlated with patient survival, which suggest CD133 promoter methylaiton pattern is a promising tool for diagnostic purposes.