ANALYSIS OF CLUSTER OF DIFFERENTIATION (CD) MARKERS IN PEDIATRIC BRAIN TUMORS CAN BE USED AS A DIAGNOSTIC AND PROGNOSTIC TOOL

BACKGROUND: Malignant pediatric brain tumors constitute a heterogeneic group of central nervous system tumors, and general markers of diagnosis and prognosis are not available. Recently, a panel of CD markers (CD15, CD24, CD29) was used to define increasing neural differentiation of embryonic stem cells. Although these CD markers have been associated with worse prognosis due to presence of tumor propagating cells, alterations in adhesion and migration in various cancer types, no studies of multiple CD markers in pediatric brain tumors have been performed. METHODS: We have collected tumors, including medulloblastomas (MB), ependymomas (EP) and juvenile astrocytomas, from >20 pediatric brain tumor patients. Frozen tumor sections and cultured tumor cells were stained for CD15, CD24 and CD29 and analyzed using fluorescence microscopy or flowcytometry. RESULTS: MB contained a mixture of cells with strong CD15 labeling inside vessels and cells with diffuse CD15 staining in the parenchyma of the tumor tissue. Cells strongly labeled with CD15 were also positive for the leukocyte marker CD45. The previously proposed association between CD15 expression and prognosis in MB could instead of reflecting abundance of tumor propagating cells depend on infiltrating immune cells. In low-grade pediatric tumors and EP, larger areas stained weakly for CD15 while few cells displayed strong staining. CD24 was expressed on the vast majority of cells in pediatric brain tumors, despite grade of malignancy. MB, however, displayed an intense and aberrant staining for CD24. Computerized image analysis of frozen tumor sections showed that proliferation of cells and the expression of CD29 correlated in a sub-group of MB. CONCLUSIONS: Our preliminary data show that CD15, CD24 and CD29 are differentially expressed in high- and low-malignant pediatric brain tumors in vivo. By defining the patterns of CD antigen expression in different pediatric tumors their relationship to biological behavior and thus prognosis can be established