title: TP53 gene status and human papilloma virus infection in response to platinum plus taxane-based chemotherapy of epithelial ovarian carcinomas.
abstract: OBJECTIVE
  Lack of symptoms in early stages of disease and resistance to chemotherapy make epithelial ovarian carcinomas one of the most lethal neoplasms among gynaecological malignancies. The aim of this study was to analyse the impact of TP53 mutations, codon 72 polymorphism and human papillomavirus (HPV) infection on the response to platinum-taxane combination chemotherapy in patients with epithelial ovarian carcinomas.
  
  
  METHODS
  The study was conducted on 26 ovarian carcinoma patients who received carboplatin plus paclitaxel combination chemotherapy. DNA was isolated by salting-out procedure. Mutations in exons 4-8 of TP53 gene were detected by PCR-SSCP and confirmed by automatic DNA sequencing. Codon 72 polymorphism was assessed by the RFLP method. HPV infection was detected through amplification of one part of L1 viral gene. Genotyping was performed by DNA sequencing. Fisher's exact and log-rank tests were used for statistical analysis.
  
  
  RESULTS
  TP53 mutations were present in 5/26 (19.2%) ovarian carcinomas. The distribution of codon 72 TP53 genotypes was: Arg/Arg 38.5%, Arg/Pro 50.0%, Pro/Pro 11.5%. HPV was present in 4/26 (15.4%) ovarian carcinomas. All HPV-positive tumors were HPV16 type. Patients with mutations in TP53 gene, Arg/Arg genotype of codon 72 and absence of HPV infection experienced the highest tumor response rate to platinum-taxane chemotherapy. However, no significant correlation between progression free interval (PFI) and the examined biomarkers was observed.
  
  
  CONCLUSIONS
  Our results indicate that, based on the TP53 gene status and the presence/absence of HPV infection, the subgroups of patients having better initial response to platinum-taxane therapy could be distinguished. This might contribute to more adequate treatment and individual therapeutic approach.
authors.affiliation: Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia. eminamalisic@yahoo.co.uk
authors.forename: E
authors.initials: E
authors.lastname: Malisic
authors.forename: R
authors.initials: R
authors.lastname: Jankovic
authors.forename: K
authors.initials: K
authors.lastname: Jakovljevic
authors.forename: S
authors.initials: S
authors.lastname: Radulovic
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001483:Base Sequence; D016190:Carboplatin / Q000008:administration & dosage; D000077216:Carcinoma, Ovarian Epithelial; D003062:Codon; D004273:DNA, Neoplasm / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D016158:Genes, p53; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000821:virology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000821:virology; D017239:Paclitaxel / Q000008:administration & dosage; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications* / Q000235:genetics / Q000821:virology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D003062:Codon; D004273:DNA, Neoplasm; D016190:Carboplatin; D017239:Paclitaxel