title: TP53 mutations in prostatic cancer. Analysis of pre- and post-treatment archival formalin-fixed tumour tissue.
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.
authors.affiliation: Department of Pathology, Norwegian Radium Hospital, Oslo.
authors.forename: A
authors.initials: A
authors.lastname: Berner
authors.forename: G
authors.initials: G
authors.lastname: Geitvik
authors.forename: F
authors.initials: F
authors.lastname: Karlsen
authors.forename: S D
authors.initials: SD
authors.lastname: Fosså
authors.forename: J M
authors.initials: JM
authors.lastname: Nesland
authors.forename: A L
authors.initials: AL
authors.lastname: Børresen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004586:Electrophoresis; D005557:Formaldehyde; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D016707:Tissue Fixation; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D005557:Formaldehyde