p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study.

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Kang, Eun-Young 
Rambau, Peter F 
Lee, Cheng-Han 

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.


Funder: Cancer Council Victoria; Id: http://dx.doi.org/10.13039/501100000951

Funder: Queensland Cancer Fund

Funder: Cancer Council New South Wales; Id: http://dx.doi.org/10.13039/501100001102

Funder: Cancer Council South Australia; Id: http://dx.doi.org/10.13039/501100000950

Funder: Cancer Foundation of Western Australia

Funder: Cancer Council Tasmania; Id: http://dx.doi.org/10.13039/501100001169

Funder: Peter MacCallum Foundation; Id: http://dx.doi.org/10.13039/501100022084

Funder: Ovarian Cancer Australia; Id: http://dx.doi.org/10.13039/100011928

Funder: ELAN Funds of the University of Erlangen‐Nuremberg

Funder: Breast Cancer Now; Id: http://dx.doi.org/10.13039/100009794

Funder: Institute of Cancer Research

Funder: NHS

Funder: Biomedical Research Centre

Funder: Fondo Europeo de Desarrollo Regional; Id: http://dx.doi.org/10.13039/501100008530

Funder: German Cancer Research Center; Id: http://dx.doi.org/10.13039/100008658

Funder: Mayo Foundation; Id: http://dx.doi.org/10.13039/100007048

Funder: Minnesota Ovarian Cancer Alliance; Id: http://dx.doi.org/10.13039/100003135

Funder: Fred C. and Katherine B. Andersen Foundation; Id: http://dx.doi.org/10.13039/100017909

Funder: Pomeranian Medical University; Id: http://dx.doi.org/10.13039/501100008781

Funder: UK National Institute for Health Research

Funder: University of Cambridge; Id: http://dx.doi.org/10.13039/501100000735

Funder: Clinical Academic Reserve

Funder: Oak Foundation; Id: http://dx.doi.org/10.13039/100001275

Funder: National Institute for Health Research; Id: http://dx.doi.org/10.13039/501100000272

Funder: University College London Hospitals Biomedical Research Centre

Funder: The BC Cancer Foundation

Funder: VGH and UBC Hospital Foundation; Id: http://dx.doi.org/10.13039/100014823

Funder: Cancer Institute NSW; Id: http://dx.doi.org/10.13039/501100001171

Funder: Sydney West Translational Cancer Research Centre; Id: http://dx.doi.org/10.13039/100013121

TP53, clear cell, endometrioid, high-grade serous carcinoma, ovarian cancer, p53, prognosis, Humans, Female, Tumor Suppressor Protein p53, Ovarian Neoplasms, Carcinoma, Ovarian Epithelial, Carcinoma, Endometrioid
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J Pathol Clin Res
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Cancer Research UK (A22905)
National Institute for Health Research (IS-BRC-1215-20014)
Cancer Research UK (A25117)