Article
Tissue Microarray (TMA)-based expression analysis of tumor stem cell markers compared to clinical outcome of glioma patients
Gewebechip-basierte Expressionsanalysen von Tumorstammzellmarkern in Gliomen
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Published: | May 30, 2008 |
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Objective: Gliomas are heterogeneous tumors with an unpredictable clinical course. An increasing body of research is showing that tumors contain their own stem cells. Stem cell-like cancer cells were isolated from gliomas and are presumed to be responsible for therapy resistance. The aim of this study was to correlate the expression pattern of known stem cell markers on a TMA containing samples of astrocytic gliomas with patient outcome.
Methods: 331 Paraffin embedded tumor samples from 292 Patients including 39 recurrent tumors as well as 11 pilocytic astrocytomas WHO I°, 41 low grade gliomas WHO II°, 21 anaplastic astrocytomas WHO III° and 258 glioblastomas WHO IV were gathered and available as a TMA. Clinical data regarding survival rates and treatment regimens were assessed in a data base. The TMA was used for immunohistochemical staining of Nestin, Musashi, and Sox-2. Survival data were computed using a multivariate Cox proportional hazard model.
Results: Proportion of Nestin-positive cells increased with tumor grade and correlated with a worse patient survival. However, when applying a multivariate survival analysis including WHO grade, patient age and extent of resection, Nestin expression showed a significant correlation with a shorter time to malignant progression (p=0.45). Moreover, expression of Musashi was also augmented with increasing tumor grade and in addition correlated significantly with a shorter overall survival in multivariate analysis (p=0.024). Only Sox-2 expression did not change significantly with tumor grade and also did not correlate with patient outcome.
Conclusions: Our findings on Nestin and Musashi expression support the current cancer stem cell hypothesis and the assumption that these cells are involved in therapy resistance.