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

Abstract

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. Materials and 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. Conclusion: 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.