Genetic sub-types of human malignant astrocytoma correlate with survival

Abstract

In human malignant astrocytoma, age of the patient and histological grade of the tumor are important prognostic variables. Several genetic changes have been reported to occur in these tumors, which may be of additional and independent prognostic relevance. To determine their prognostic significance, we analyzed 75 high-grade tumors, 12 anaplastic astrocytomas and 63 glioblastomas multiforme, for the presence of genetic changes that occur frequently in high-grade astrocytoma, i.e., loss of heterozygosity (LOH) for chromosome 10, p53, gene alteration (mutation and/or LOH), and EGFR-gene amplification. We defined 4 groups of patients who showed a specific combination of genetic changes in the tumor: group 1, p53-gene alteration without complete LOH 10; group 2, complete LOH 10 only; group 3, p53-gene alteration + complete LOH 10; group 4, complete LOH 10 + EGFR-gene amplification. In univariate analysis, the log-rank test revealed significant differences in survival between patients of group 1 (median survival of 13 months) and group 3 (median survival of 5.2 months, p = 0.0058) and between patients of group 1 and group 4 (median survival of 4 months, p = 0.0033). In multivariate analysis, age and genetic sub-type proved to be important prognostic variables, whereas histological grading was less important. The age-corrected survival time for group-4 patients is significantly shorter than that for group-1 patients (relative risk = 3.79, p = 0.0075). Our data indicate that genetic sub-type is an important prognostic variable in human high-grade astrocytoma.