Prognostic Relevance of c-Myc and Bmi-1 Expression in Patients with Glioblastoma Multiforme
Tonia Cenci, Maurizio Martini, Nicola Montano, Sara Capodimonti, Roberto Pallini, Luigi M Larocca. Università Cattolica del Sacro Cuore, Rome, Italy
Background: Although the c-Myc oncogene is one of the most important and frequently deregulated proteins in different human tumors playing a central role in cell growth and apoptosis, the involvement of this gene in the pathogenesis of glioblastoma multiforme is not clear and still debated.
Design: We have analyzed the expression of c-Myc, Bmi-1 and H3K9ac, using immunohistochemistry, in 48 patients with glioblastoma multiforme (GBM) and in 20 normal brain tissues. After surgical treatment, all GBMs were subjected to adjuvant radiotherapy with concomitant administration of temozolomide. Protein expressions were correlated with clinical characteristics and outcome.
Results: We found that overexpression of c-Myc were significantly associated to Bmi-1expression (p=0.009). c-Myc and Bmi-1 overexpression was significantly associated to longer overall survival (p<0.0001 and p=0.0009, respectively). In addition, within unmethyled MGMT cases treated with TZM, GBMs overexpressing c-Myc showed a better prognosis in comparison to GBMs with normal of low expression of c-Myc (p<0.0001). Conversely, H3K9ac expression showed no significant association to any biological and clinical features. Multivariate analysis considering c-Myc, Bmi-1, MGMT methylation status, age, sex, Ki-67 and KPS, as variables, showed that c-Myc (p=0.022), Ki-67 (p=0,036), MGMT (p=0.05) and KPS (p=0,017) were significant predictors for favorable outcome.
Conclusions: Our results seem to reinforce the recently formulated hypothesis that c-Myc and associated genes, such as Bmi-1, could have a role in the sensitization of cancer cells towards several chemotherapeutic agents, such as TZM, probably through the activation of different apoptotic pathways.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 247, Tuesday Afternoon