P53 gene status in patients with advanced serous epithelial ovarian cancer in relation to response to paclitaxel- plus platinum-based chemotherapy and long-term clinical outcome.
BACKGROUND
The aim of this retrospective study was to assess whether p53 gene status has any predictive or prognostic relevance in patients with advanced, poorly-differentiated serous epithelial ovarian cancer treated with paclitaxel- plus platinum-based chemotherapy.


METHODS
The study was conducted on 46 patients who underwent surgery followed by paclitaxel- plus carboplatin-based chemotherapy. The tumor tissue samples were analyzed for p53 gene mutations. The median follow-up of survivors was 50.3 months.


RESULTS
Twenty-three patients (50%) showed p53 mutations at exons 5 to 9. Sixteen (34.8%) patients had a polymorphism at codon 72 in exon 4 (SNP codon 72): 10 were Pro/Pro homozygous and 6 Pro/Arg heterozygous. Four polymorphic patients had a second mutation at exons 5 to 9. An inverse correlation was evidenced between the SNP codon 72 and mutations at exons 5 to 9, with the latter more frequently found in wild-type (Arg/Arg) codon 72 (19/30 versus 4/16, 63.3% versus 25.0%; p=0.03) cases. A clear trend for a higher response rate and longer progression-free and overall survival was observed in wild-type p53 and Pro/Pro polymorphic patients as compared to patients with mutant p53.


CONCLUSIONS
The addition of paclitaxel to carboplatin does not appear to overcome the negative predictive and prognostic significance of p53 gene mutations in serous ovarian cancer. Nevertheless, the comprehensive analysis of p53 genotype, including the SNP codon 72, warrants further investigation in order to envisage individual responsiveness to cancer therapy.
Gadducci
Angiolo
A
Department of Procreative Medicine, Division of Gynecology and Obstetrics, University of Pisa, Italy. a.gadducci@obgyn.med.unipi.it
Di Cristofano
Claudio
C
Zavaglia
Michele
M
Giusti
Laura
L
Menicagli
Michele
M
Cosio
Stefania
S
Naccarato
Antonio G
AG
Genazzani
Andrea R
AR
Bevilacqua
Generoso
G
Cavazzana
Andrea O
AO
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005091:Exons; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D011110:Polymorphism, Genetic; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D017239:Paclitaxel