Analysis of complex relationships between age, p53, epidermal growth factor receptor, and survival in glioblastoma patients

Glioblastoma multiforme (GBM) carries a dismal prognosis. However, a range of survival times exists, and parameters that define prognostic groups may help to optimize treatment. To identify such prognostic groups, we analyzed tumor tissue from 110 cases of newly diagnosed GEM from two clinical proto cols. Similar to other studies, we found no association of epidermal growth factor receptor (EGFR) overexpression (as assessed by immunohistochemistry ), p53 immunopositivity, or p53 mutation with survival in the entire sample , However, EGFR overexpression showed trends toward worse prognosis in pati ents younger than the median age, but better prognosis in patients older th an the median age. This interaction of EGFR with age group was statisticall y significant and led us to focus our further analyses on the younger patie nts. In this group, a statistically significant association of EGFR overexp ression with worse survival was identified in the p53-negative but not p53- positive tumors. We found a similar result after screening these cases for mutations in p53: EGFR overexpression was negatively associated with surviv al only in the p53 wild-type cases. To confirm this unexpected result, this finding was reproduced in a validation sample of an additional 42 tumors f rom younger patients on the same two clinical protocols. This complex relat ionship between EGFR and p53 in younger patients remained in a multivariate analysis that incorporated additional prognostic variables. The results su ggest that analysis of prognostic markers in GEM is complex, and maximal in formation may require analysis of subgroups based on age and the status of specific markers such as p53, In addition, they suggest a specific group of patients on which to focus promising therapies targeting EGFR.