Funder: Biomedical Research CentreFunder: European Regional Development FundFunder: Mayo Foundation for Medical Education and ResearchFunder: Pomeranian Medical UniversityFunder: Pomorski Uniwersytet Medyczny W SzczecinieFunder: Cancer Council NSWFunder: Cancer Institute NSWFunder: Deutsches KrebsforschungszentrumFunder: The BC Cancer FoundationFunder: University College London Hospitals Biomedical Research CentreFunder: Breast Cancer NowFunder: Cancer Council TasmaniaFunder: Clinical Academic ReserveFunder: ELAN Funds of the University of Erlangen-NurembergFunder: Fondo Europeo de Desarrollo RegionalFunder: National Institute for Health Research (NIHR)Funder: National Institute for Health and Care ResearchFunder: Ovarian Cancer AustraliaFunder: Queensland Cancer FundFunder: Cancer Council New South WalesFunder: Fred C. and Katherine B. Andersen FoundationFunder: German Cancer Research CenterFunder: Institute of Cancer ResearchFunder: Mayo FoundationFunder: Minnesota Ovarian Cancer AllianceFunder: Peter MacCallum FoundationFunder: University of CambridgeFunder: Cancer Foundation of Western AustraliaFunder: VGH and UBC Hospital FoundationFunder: Cancer Council VictoriaFunder: NHSFunder: UK National Institute for Health ResearchFunder: Cancer Council South AustraliaFunder: Oak FoundationFunder: Sydney West Translational Cancer Research CentreOur objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC
