PTEN mutation, EGFR amplification, and outcome in patients with anaplasticastrocytoma and glioblastoma multiforme

Background. Survival of patients with anaplastic astrocytoma is highly vari able. Prognostic markers would thus be useful to identify clinical subsets of such patients. Because specific genetic alterations have been associated with glioblastoma, we investigated whether similar genetic alterations cou ld be detected in patients with anaplastic astrocytoma and used to identify those with particularly aggressive disease. Methods: Tissue specimens were collected from 174 patients enrolled in Mayo Clinic Cancer Center and Nort h Central Cancer Treatment Group clinical trials for newly diagnosed glioma s, including 63 with anaplastic astrocytoma. and III with glioblastoma mult iforme. Alterations of the EGFR, PTEN, and p53 genes and of chromosomes 7 a nd 10 were examined by fluorescence in situ hybridization, semiquantitative polymerase chain reaction, and DNA sequencing. All statistical tests were two-sided. Results: Mutation of PTEN, amplification of EGFR, and loss of th e q arm of chromosome 10 were statistically significantly less common in an aplastic astrocytoma than in glioblastoma multiforme (P =.033, P =.001, and P < .001, respectively), and mutation of p53 was statistically significant ly more common (P < .001). Univariate survival analyses of patients with an aplastic astrocytoma identified PTEN (P =.002) and p53 (P =.012) mutations as statistically significantly associated with reduced and prolonged surviv al, respectively. Multivariate Cox analysis of patients with anaplastic ast rocytoma showed that PTEN mutation remained a powerful prognostic factor af ter adjusting for patient age, on-study performance score, and extent of tu mor resection (hazard ratio = 4.34; 95% confidence interval = 1.82 to 10.34 ). Multivariate classification and regression-tree analysis of all 174 pati ents identified EGFR amplification as an independent predictor of prolonged survival in patients with glioblastoma multiforme who were older than 60 y ears of age. Conclusion: PTEN mutation and EGFR amplification are important prognostic factors in patients with anaplastic astrocytoma and in older pa tients with glioblastoma multiforme, respectively.