SOX2 Expression and EGFR Amplification Are Present in the Invasive Border of Glioblastoma and Could Be Used as Good Markers To Differentiate Tumor Cells from Reactive Glia.
Miguel A Idoate, Ricardo Diez Valle, Jose Echeveste, Rafael Carias, Maria Dolores Lozano, Susana Inoges. University of Navarra, Pamplona, Spain
Background: We have previously shown that surgery done with 5-ala fluorescence allows highly precise separate sampling of the invasive border of the tumor in glioblastoma (GBM). In the border of GBM, the tumor cells have a mature aspect rather similar to reactive glia and discriminative markers between tumor cells and reactive glia are necessary. Sox2 is considered a marker of precursor cell and could be used as a good marker of tumor cells. By other way, EGFR amplification is a characteristic molecular alteration in GBM. However, it is not known how is the expression of these markers in the border of GBM and in the reactive glia.
Design: In 20 GBM the fluorescent quality of the tissue was used to take biopsies from the tumor center and the periphery. Only GBM with EGFR amplification were considered for this study. First, the EGFR amplification and the Sox2 and GFAP expression were evaluated by silver in-situ hybridization (SISH) and immunohistochemistry, respectively. These markers were compared between the center and the border of GBM. Second, these results were compared with the reactive glia in 19 cases of both vascular malformations and mesial temporal gliosis. As a control group, several representative samples of both center and border of GBM were cultured in a conventional medium and suspension cells were obtained and tested in a similar way. Non-parametrical statistical studies were applied.
Results: In 19/20 GBM, central tumor areas showed an intense nuclear staining in tumor cells against Sox2, but not in vessels or inflammatory cells. In the border of GBM, the expression of Sox2 was very similar, with no o scarce cytoplasmic expression. EGFR strong amplification similar to the center of the tumor was detected in every case in tumor cells from the periphery. The density of both amplified EGFR nuclei and Sox2 stained cells in the periphery correlated in most of cases (p<0,005). However, in the reactive glia, Sox2 was only cytoplasmic and less intense than in tumor cells and no EGFR amplification was detected at all. Interestingly, in the culture group, EGFR amplification was not detected and Sox2 was reduced, while the GFAP staining was preserved.
Conclusions: In the border of GBM, Sox2 expression and EGFR amplification are preserved and could be used as good markers to differentiate the peripheral tumor cells from the reactive glia.
Tuesday, March 1, 2011 1:45 PM
Platform Session: Section G, Tuesday Afternoon