ABSTRACT
UNLABELLED: As the value of grading of ependymomas is currently debated we studied the expression of proliferation- and apoptosis-related proteins in these tumors as these mechanisms both are suggested to be important in tumor growth. We characterized the immunohistochemical expression of p53, Mdm2, Bcl-2, and Bax in 51 intracranial ependymomas. We also assessed the apoptosis- and proliferation-index, measured by MIB-1, PCNA-immunohistochemistry, and analyzed the clinical parameters. Of all used antibodies, the correlation with survival and the correlation among ordered categories was assessed. None of the analyzed immunohistochemical variables were significantly correlated with tumor grade. On the other hand, PCNA, MIB-1, and p53 were significantly related to the survival of the patient. In multivariate analysis, p53 was the only independent predictive variable (p = 0.0132). CONCLUSION: The strongest predictors of survival in univariate analysis were the expression of PCNA, MIB-1 and p53. In multivariate analysis a p53 expression > 1% showed to be significantly related with a worse survival. The predicting value of p53 expression has to be confirmed by others before solid conclusions can be made. Apoptosis seems not to be an important mechanism in tumor growth in ependymomas. The expression of Mdm2, Bcl-2, and Bax were not related to survival.
Subject(s)
Apoptosis , Brain Neoplasms/chemistry , Brain Neoplasms/mortality , Ependymoma/chemistry , Ependymoma/mortality , Adolescent , Adult , Aged , Antigens, Nuclear , Brain Neoplasms/pathology , Cell Division , Child , Child, Preschool , Ependymoma/pathology , Female , Humans , Immunohistochemistry , Infant , Ki-67 Antigen , Male , Middle Aged , Nuclear Proteins/analysis , Predictive Value of Tests , Proliferating Cell Nuclear Antigen/analysis , Proto-Oncogene Proteins/analysis , Proto-Oncogene Proteins c-bcl-2/analysis , Survival Analysis , Tumor Suppressor Protein p53/analysis , bcl-2-Associated X ProteinABSTRACT
Serial analysis of gene expression (SAGE) was used to identify a gene named GOA (gene overexpressed in astrocytoma), which codes for a novel Ring finger B-box coiled-coil (RBCC) protein. Northern blot hybridization showed overexpression of GOA in 9 of 10 astrocytomas. Except for kidney, in which high expression was found, expression levels in normal tissues were low and comparable to normal brain. Immunohistochemistry demonstrated presence of GOA, with prominent nuclear staining, in astrocytoma tumor cells and astrocytes of fetal brain, but virtual absence in mature astrocytes. Overexpression was not due to amplification, since amplification of GOA was only found in one of 65 astrocytomas. GOA was localized to 17q24-25, a region that is frequently gained or amplified in a number of other tumor types. GOA contains two LXXLL motifs, which are thought to be important for nuclear receptor binding. Our data suggest an important role of GOA in the process of dedifferentiation that is associated with astrocytoma tumorigenesis and possibly with that of other tumor types as well.
