GENETIC SUBTYPES OF HUMAN-MALIGNANT ASTROCYTOMA CORRELATE WITH SURVIVAL

In human malignant astrocytoma, age of the patient and histological gr ade of the tumor are important prognostic variables. Several genetic c hanges have been reported to occur in these tumors, which may be of ad ditional and independent prognostic relevance. To determine their prog nostic significance, we analyzed 75 high-grade tumors, 12 anaplastic a strocytomas and 63 glioblastomas multiforme, for the presence of genet ic changes that occur frequently in high-grade astrocytoma, i.e., loss of heterozygosity (LOH) for chromosome 10, p53-gene alteration (mutat ion and/or LOH), and EGFR-gene amplification. We defined 4 groups of p atients who showed a specific combination of genetic changes in the tu mor: group I, p53-gene alteration without complete LOH 10; group 2, co mplete LOH 10 only; group 3, p53-gene alteration + complete LOH 10; gr oup 4, complete LOH 10 + EGFR-gene amplification. In univariate analys is, the log-rank test revealed significant differences in survival bet ween patients of group I (median survival of 13 months) and group 3 (m edian survival of 5.2 months, p = 0.0058) and between patients of grou p 1 and group 4 (median survival of 4 months, p = 0.0033). In multivar iate analysis, age and genetic sub-type proved to be important prognos tic variables, whereas histo logical grading was less important. The a ge-corrected survival time for group-4 patients is significantly short er than that for group-1 patients (relative risk = 3.79, p = 0.0075). Our data indicate that genetic sub-type is an important prognostic var iable in human high-grade astrocytoma. (C) 1998 Wiley-Liss, Inc.