TP53 MUTATIONS IN PROSTATIC-CANCER - ANALYSIS OF PRETREATMENT AND POSTTREATMENT ARCHIVAL FORMALIN-FIXED TUMOR-TISSUE

The TP53 gene mutation pattern in prostatic cancer was examined in rel ation to progression and survival, using archival farmalin-fixed pre- and post-treatment tumour specimens from 84 prostatic cancer patients. Thirty-four had hormone-sensitive tumours and 50 were hormone-resista nt. Six of the 34 (18 per cent) therapy-responding tumours and 19 of t he 50 (38 per cent) hormone-resistant tumours showed p53 protein accum ulation in the post-treatment specimen. Both pre- and post-treatment s pecimens from these 25 patients were analysed for mutation of the cons erved regions of the TP53 gene (exons 5-8), using constant denaturant gel electrophoresis (CDGE) followed by DNA sequencing. In the post-tre atment samples, mutations were detected in three of the six patients w ith hormone-responsive tumours and in 11 of the 19 patients with hormo ne-resistant tumours. The three (100 per cent) patients with therapy-r esponsive tumours with mutations and nine of the 11 (82 per cent) pati ents with therapy-resistant tumours with mutations died of the disease . Thirteen of the 14 mutations in the post-treatment specimens were tr ansitions, 11 occurring at CpG dinucleotides in which codon 273 was in volved in ten. A significantly higher proportion of tumours with mutat ions were poorly differentiated compared with tumours without mutation (P<0.04). Our findings indicate that TP53 mutation is a late event in tumour development of the prostate gland and that codon 273 might be a 'hotspot' for mutation in the progression of the disease.