TP53 ALTERATIONS AND CLINICAL OUTCOME IN LOW-GRADE ASTROCYTOMAS

Thirty-eight WHO grade II astrocytomas and 10 malignant recurrent glio mas in these patients were examined for the presence of TP53 alteratio ns. Seventeen/38 low grade astrocytomas and 6/10 malignant recurrent t umors harbored mutations of the gene detected by SSCP analysis and dir ect sequencing of PCR products. TP53 mutations in five out of six high grade mutant tumors were already present in the corresponding low gra de astrocytomas. In two cases, TP53 mutations present in the low grade astrocytoma could not be demonstrated in the recurrent glioma. Immuno histochemistry with two different antibodies to the human TP53 protein revealed nuclear immunoreaction of tumor cells in 11/38 low grade and in 8/10 recurrent tumors. There was no correlation between the presen ce of TP53 alteration and clinical course. We conclude that, although TP53 mutations are detectable in a substantial fraction of WHO grade I I astrocytomas, they do not appear to play a role in the malignant pro gression of these tumors and they are not of prognostic significance. (C) 1994 Wiley-Liss, Inc.