P53 Mutations in Tissue From Danish Ovarian Cancer Patients: From the Danish "MALOVA" Ovarian Cancer Study

Gynecol Oncol. 2006 Jan;100(1):76-82. doi: 10.1016/j.ygyno.2005.07.131. Epub 2005 Sep 23.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CA-125 Antigen / blood
  • Denmark
  • Female
  • Gene Deletion
  • Genes, p53 / genetics*
  • Humans
  • Lectins, C-Type / blood
  • Middle Aged
  • Mutation, Missense*
  • Neoplasm Staging
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Polymorphism, Genetic
  • Proportional Hazards Models

Substances

  • CA-125 Antigen
  • Lectins, C-Type
  • tetranectin