P53 mutations in tissue from Danish ovarian cancer patients: from the Danish "MALOVA" ovarian cancer study

OBJECTIVES: The p53 gene, a tumor suppressor gene located on the short arm of chromosome 17 (17p13), has been found mutated in 30-80% of epithelial ovarian cancers (OC), with the most frequently detected mutations in the conserved regions of the gene. A small number of studies investigated the survival of patients with p53 mutations in OC, but their conclusions are not in agreement.

METHODS: We analyzed the frequency of p53 mutations in 124 Danish women with OC, using Single-Stranded Conformation Polymorphism analysis in addition with DNA sequencing and evaluated if mutations correlated with clinicopathological parameters and with patient survival.

RESULTS: Thirty-five (28%) ovarian tumors were found to contain one or more p53 variations, two of which were considered polymorphisms. Twenty-seven (82%) mutations were single nucleotide substitutions of which 23 (85%) were missense mutations and therefore led to amino acid substitutions. Significantly shorter survival was found for stage III/IV patients with a p53 missense mutation compared to stage III/IV OC patients with wild type p53 (P = 0.0018). Multivariate Cox regression analysis restricted to 107 OC patients with a p53 missense mutation or p53 wild type in the tumor tissue and with information on radicality of primary surgery showed that missense p53 mutation (HR = 2.5, 95% CI: 1.21-4.98), radicality after primary surgery (HR = 1.7, 95% CI: 1.04-2.88), tetranectin (mg/l: HR = 0.78, 95% CI: 0.67-0.91) and stage (I vs. III: HR = 0.30, 95% CI: 0.10-0.92, II vs. III: HR = 0.24, 95% CI: 0.05-1.05, IV vs. III: HR = 2.70, 95% CI: 1.22-5.98) were independent prognostic factors.

CONCLUSION: Missense mutations in the conserved regions of p53 may be of prognostic value in Danish OC patients.