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, 176 (3), 299-308

TP53 Mutations in Prostatic Cancer. Analysis of Pre- And Post-Treatment Archival Formalin-Fixed Tumour Tissue

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TP53 Mutations in Prostatic Cancer. Analysis of Pre- And Post-Treatment Archival Formalin-Fixed Tumour Tissue

A Berner et al. J Pathol.

Abstract

The TP53 gene mutation pattern in prostatic cancer was examined in relation to progression and survival, using archival formalin-fixed pre- and post-treatment tumour specimens from 84 prostatic cancer patients. Thirty-four had hormone-sensitive tumours and 50 were hormone-resistant. Six of the 34 (18 per cent) therapy-responding tumours and 19 of the 50 (38 per cent) hormone-resistant tumours showed p53 protein accumulation in the post-treatment specimen. Both pre- and post-treatment specimens from these 25 patients were analysed for mutation of the conserved regions of the TP53 gene (exons 5-8), using constant denaturant gel electrophoresis (CDGE) followed by DNA sequencing. In the post-treatment samples, mutations were detected in three of the six patients with hormone-responsive tumours and in 11 of the 19 patients with hormone-resistant tumours. The three (100 per cent) patients with therapy-responsive tumours with mutations and nine of the 11 (82 per cent) patients with therapy-resistant tumours with mutations died of the disease. Thirteen of the 14 mutations in the post-treatment specimens were transitions, 11 occurring at CpG dinucleotides in which codon 273 was involved in ten. A significantly higher proportion of tumours with mutations 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.

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