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.