p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study.
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Our 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.
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Funder: Biomedical Research Centre
Funder: European Regional Development Fund
Funder: Mayo Foundation for Medical Education and Research
Funder: Pomeranian Medical University
Funder: Pomorski Uniwersytet Medyczny W Szczecinie
Funder: Cancer Council NSW
Funder: Cancer Institute NSW
Funder: Deutsches Krebsforschungszentrum
Funder: The BC Cancer Foundation
Funder: University College London Hospitals Biomedical Research Centre
Funder: Breast Cancer Now
Funder: Cancer Council Tasmania
Funder: Clinical Academic Reserve
Funder: ELAN Funds of the University of Erlangen-Nuremberg
Funder: Fondo Europeo de Desarrollo Regional
Funder: National Institute for Health Research (NIHR)
Funder: National Institute for Health and Care Research
Funder: Ovarian Cancer Australia
Funder: Queensland Cancer Fund
Funder: Cancer Council New South Wales
Funder: Fred C. and Katherine B. Andersen Foundation
Funder: German Cancer Research Center
Funder: Institute of Cancer Research
Funder: Mayo Foundation
Funder: Minnesota Ovarian Cancer Alliance
Funder: Peter MacCallum Foundation
Funder: University of Cambridge
Funder: Cancer Foundation of Western Australia
Funder: VGH and UBC Hospital Foundation
Funder: Cancer Council Victoria
Funder: NHS
Funder: UK National Institute for Health Research
Funder: Cancer Council South Australia
Funder: Oak Foundation
Funder: Sydney West Translational Cancer Research Centre
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2056-4538
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National Institute for Health and Care Research (IS-BRC-1215-20014)
Cancer Research UK (A25117)