BCL-2 FAMILY PROTEIN EXPRESSION IN HUMAN-MALIGNANT GLIOMA - A CLINICAL-PATHOLOGICAL CORRELATIVE STUDY

Malignant gliomas are rather refractory to current therapeutic approac hes including surgery, radiotherapy, chemotherapy and immunotherapy. A cquired alterations in the pathways required for apoptotic cell death are thought to be responsible to the failure of glioma to respond to t herapy, Here we have examined the expression of several proteins invol ved in the susceptibility to apoptosis in 20 human gliomas, including the BCL-2 family proteins BCL-2, BCL-X, BAX and MCL-1, as well as p53 and RE. Most gliomas expressed several BCL-2 family proteins. There wa s good correlation between expression of the functional antagonists, B CL-2/BCL-X and BAX, suggesting that changes in the BCL-2+BCL-X/BAX rat io are not responsible for the differential response of glioma patient s to chemotherapy. The immunochemistry data were also analysed in rega rd to response to therapy and clinical outcome. All patients had cytor eductive surgery and received radiotherapy and nitrosourea-based adjuv ant chemotherapy. There was no prominent association of outcome with t he expression patterns of p53, RB, BCL-2, BCL-X or BAX. We find, howev er, that expression of the MCL-1 protein is associated with early tumo ur recurrence and, shorter survival in this group of glioma patients. This preliminary observation will have to be confirmed in a larger ind ependent sample of glioma patients. (C) 1998 Elsevier Science B.V.