Molecular Diagnostics
British Journal of Cancer (2006) 95, 627–633. doi:10.1038/sj.bjc.6603300 www.bjcancer.com
Published online 1 August 2006
Factors influencing p53 expression in ovarian cancer as a biomarker of clinical outcome in multicentre studies
P de Graeff1,7, J Hall2,7, A P G Crijns1, G H de Bock3, J Paul2, K A Oien2, K A ten Hoor1, S de Jong4, H Hollema5, J M S Bartlett6, R Brown2,8 and A G J van der Zee1
- 1Department of Gynaecologic Oncology, University Medical Centre Groningen, University of Groningen, Groningen 9700 RB, The Netherlands
- 2Centre for Oncology and Applied Pharmacology, Cancer Research UK Beatson Laboratories, University of Glasgow, Garscube Estate, Glasgow G61 1BD, UK
- 3Department of Epidemiology and Statistics, University Medical Centre Groningen, University of Groningen, Groningen 9700 RB, The Netherlands
- 4Department of Medical Oncology, University Medical Centre Groningen; University of Groningen, Groningen 9700 RB, The Netherlands
- 5Department of Pathology, University Medical Centre Groningen, University of Groningen, Groningen 9700 RB, The Netherlands
- 6Endocrine Cancer Group, University Department of Surgery, Royal Infirmary, Glasgow G31 2ER, UK
Correspondence: Professor R Brown, E-mail: r.brown@beatson.gla.ac.uk
7These authors contributed equally to this work.
8On behalf of the Scottish Gynaecological Clinical Trials Group
Revised 30 May 2006; Accepted 29 June 2006; Published online 1 August 2006.
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.
Keywords:
ovarian cancer, prognosis, p53
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