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


CONCLUSIONS
Missense mutations in the conserved regions of p53 may be of prognostic value in Danish OC patients.
Høgdall
Estrid V S
EV
Department of Virus, Hormones and Cancer, Institute of Cancer Epidemiology, Danish Cancer Society, DK-2100 Copenhagen, Denmark. hogdall@dadlnet.dk
Kjaer
Susanne K
SK
Blaakaer
Jan
J
Christensen
Lise
L
Glud
Eva
E
Vuust
Jens
J
Høgdall
Claus K
CK
D000328:Adult; D000368:Aged; D018394:CA-125 Antigen / Q000097:blood; D003718:Denmark; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D037181:Lectins, C-Type / Q000097:blood; D008875:Middle Aged; D020125:Mutation, Missense; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models
D018394:CA-125 Antigen; D037181:Lectins, C-Type; C048648:tetranectin