SOX2 expression and amplification in gliomas and glioma cell lines.

ABSTRACT

BACKGROUND: The transcription factor SOX2 controls gene expression during development and has roles in both neurogenesis and gliogenesis. MATERIALS AND METHODS: The current study utilized immunohistochemistry, immunofluorescence, molecular genetics (gene copy number analysis) and Western blotting to examine SOX2 expression in surgical samples from 133 brain gliomas of different grades of malignancy, and in cell lines from 16 glioblastomas. RESULTS: Our results reveal a positive correlation between SOX2 expression and malignancy grade in gliomas and identify the hypercellular and hyperproliferative areas of glioblastomas as the areas with the highest SOX2 expression. SOX2 gene amplification was found in neurospheres and 14.4% and 11.1% of glioblastomas and anaplastic oligodendrogliomas, respectively. In contrast, SOX2 expression was not observed in neuronal tumors and varied in medulloblastomas depending upon their neuronal differentiation status. CONCLUSION: It is concluded that SOX2 is a marker for undifferentiated and proliferating cells and that its expression is up-regulated in the most anaplastic areas of glioblastomas and oligodendrogliomas. The hypothesis is that antigenic and genetic analogy exist between these areas and neurospheres and that glioblastoma stem cells may actually be dedifferentiated tumor cells that re-acquire a stem cell-like status.