P53 EXPRESSION, MUTATION, AND ALLELIC DELETION IN OVARIAN-CANCER

The aim of this investigation was to study the prevalence of p53 gene mutations and allelic deletions in ovarian cancer and the relationship between these events and p53 expression. Genomic p53 was amplified by the polymerase chain reaction (PCR) from paraffin-embedded sections o f tumour and non-tumour tissue. Exons 5-9 were screened for mutations using non-isotopic single-strand conformation polymorphism (SSCP) anal ysis. Allelic deletions at a sequence polymorphism in exon 4 were stud ied for loss of heterozygosity (LOH) by restriction analysis and by SS CP. p53 expression was detected by immunohistochemistry with the p53 a ntibodies CM1 and Do7. Of 44 cases, ten (23 per cent), including a muc inous tumour of low malignant potential, showed mutations. There was a statistically significant correlation between p53 mutation and expres sion (P<0.01) but seven cases showed discordance. Of 18 informative ca ses, eight (44 per cent) demonstrated LOH. Mutations were identified i n three of the informative cases, two of which also had LOH. The remai ning case showed mutations in two amplicons. p53 dysfunction, as indic ated by mutation, deletion, or increased expression, is common in ovar ian cancer. There is an association between these molecular events but the exact mechanisms of p53 inactivation remain to be elucidated.