P53 MUTATION, ALLELE LOSS ON CHROMOSOME 17P, AND DNA CONTENT IN OVARIAN-CARCINOMA

The aim of this investigation was to explore the relationships between p53 mutation, DNA aneuploidy, 17p deletions, and clinical stage in ov arian cancer. Nuclear suspensions were obtained by tissue disaggregati on, stained with propidium iodide, and analysed on a Coulter EPICS Eli te flow cytometer. DNA cell cycle analysis was performed using Multicy cle software (Phoenix Flow Systems). DNA extracted from paraffin-embed ded archival carcinomas/non-tumour tissue was used as template for PCR amplification of the microsatellite dinucleotide repeat polymorphism D17S513, a locus telomeric to p53 on 17p13.1. Allele loss at D17S513 w as detected in 64.5 per cent of carcinomas (20 of 31 informative cases ). DNA aneuploidy was detected in 20 of 54 (37 per cent) carcinomas. E ight of ten cases previously shown to harbour p53 mutations showed ane uploid DNA content. Although ten other DNA aneuploid cases had shown n o p53 mutations, the results show a statistically significant associat ion between p53 mutation and DNA aneuploidy (P < 0.01). Furthermore, t he mean DNA index of the DNA aneuploid cases was significantly higher in p53 mutant cases compared with those showing no p53 mutation (P = 0 .02). There was also a significant association between p53 mutations a nd stage, between ploidy and stage, and between allelic deletions at D 17S513 or p53 and stage, but not between these allelic deletions and p loidy. p53 mutations appear to be associated with DNA aneuploidy in ov arian cancer independently of 17p deletions. p53 mutations, DNA aneupl oidy, and 17p deletions are associated with late stage.