title: Factors influencing p53 expression in ovarian cancer as a biomarker of clinical outcome in multicentre studies.
abstract: The prognostic impact of p53 immunostaining in a large series of tumours from epithelial ovarian cancer patients in a two-centre study was analysed. The study population (n=476) comprised of a retrospective series of 188 patients (Dutch cohort) and a prospective series of 288 patients (Scottish cohort) enrolled in clinical trials. P53 expression was determined by immunohistochemistry on tissue microarrays. Association with progression-free survival (PFS) and overall survival (OS) was analysed by univariate and multivariate Cox regression analysis. Aberrant p53 overexpression was significantly associated with PFS in the Dutch and Scottish cohorts (P=0.001 and 0.038, respectively), but not with OS in univariate analysis. In multivariate analysis, when the two groups were combined and account taken of clinical factors and country of origin of the cohort, p53 expression was not an independent prognostic predictor of PFS or OS. In this well-powered study with minimal methodological variability, p53 immunostaining is not an independent prognostic marker of clinical outcome in epithelial ovarian cancer. The data demonstrate the importance of methodological standardisation, particularly defining patient characteristics and survival end-point data, if biomarker data from multicentre studies are to be combined.
authors.affiliation: Department of Gynaecologic Oncology, University Medical Centre Groningen, University of Groningen, Groningen 9700 RB, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: de Graeff
authors.forename: J
authors.initials: J
authors.lastname: Hall
authors.forename: A P G
authors.initials: AP
authors.lastname: Crijns
authors.forename: G H
authors.initials: GH
authors.lastname: de Bock
authors.forename: J
authors.initials: J
authors.lastname: Paul
authors.forename: K A
authors.initials: KA
authors.lastname: Oien
authors.forename: K A
authors.initials: KA
authors.lastname: ten Hoor
authors.forename: S
authors.initials: S
authors.lastname: de Jong
authors.forename: H
authors.initials: H
authors.lastname: Hollema
authors.forename: J M S
authors.initials: JM
authors.lastname: Bartlett
authors.forename: R
authors.initials: R
authors.lastname: Brown
authors.forename: A G J
authors.initials: AG
authors.lastname: van der Zee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor; D005260:Female; D016158:Genes, p53; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53