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

Köbel M, Kang EY, Weir A, Rambau PF, Lee CH, Nelson GS, Ghatage P, Meagher NS, Riggan MJ, Alsop J, Anglesio MS, Beckmann M, Bisinotto C, Boisen M, Boros J, Brand AH, Brooks-Wilson A, Carney ME, Coulson P, Courtney-Brooks M, Cushing-Haugen KL, Cybulski C, Deen S, El-Bahrawy MA, Elishaev E, Erber R, Fereday S, Fischer A, Gayther SA, Barquin-Garcia A, Gentry-Maharaj A, Gilks BC, Gronwald H, Grube M, Harnett PR, Harris HR, Hartkopf AD, Hartmann A, Hein A, Hendley J, Hernandez BY, Huang Y, Jakubowska A, Jimenez-Linan M, Jones ME, Kennedy CJ, Kluz T, Koziak JM, Lesnock J, Lester J, Lubinski J, Longacre TA, Lycke M, Mateoiu C, McCauley BM, McGuire V, Ney B, Olawaiye A, Orsulic S, Osorio A, Paz-Ares L, Ramon Y Cajal T, Rothstein JH, Rübner M, Schoemaker MJ, Shah M, Sharma R, Sherman ME, Shvetsov YB, Singh N, Steed H, Storr SJ, Talhouk A, Traficante N, Wang C, Whittemore AS, Widschwendter M, Wilkens LR, Winham SJ, Benitez J, Berchuck A, Bowtell DD, Dos Reis FJC, Campbell I, Cook LS, DeFazio A, Doherty JA, Fasching P, Fortner RT, García MJ, Goodman MT, Goode EL, Gronwald J, Huntsman DG, Karlan BY, Kelemen LE, Kommoss S, Le ND, Martin SG, Menon U, Modugno F, Pharoah PDP, Schildkraut JM, Sieh W, Staebler A, Sundfeldt K, Swerdlow A, Ramus SJ, Brenton JD (2023)

Publication Language: English

Publication Type: Journal article, Original article

Publication year: 2023

Journal

Book Volume: 9

Pages Range: 208-222

Journal Issue: 3

DOI: 10.1002/cjp2.311

Abstract

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.

Authors with CRIS profile

Involved external institutions

Fred Hutchinson Cancer Research Center United States (USA) (US) University of Pittsburgh United States (USA) (US) University of Sydney (USYD) Australia (AU) University of British Columbia Canada (CA) Universitätsklinikum Tübingen Germany (DE) Mayo Clinic United States (USA) (US) University of Calgary Canada (CA) The Institute of Cancer Research (ICR) United Kingdom (GB) Imperial College London / The Imperial College of Science, Technology and Medicine United Kingdom (GB) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Peter MacCallum Cancer Centre Australia (AU) HM Hospitales Spain (ES) University of Hawaiʻi Cancer Center United States (USA) (US) Duke University Medical Center United States (USA) (US) University of Cambridge United Kingdom (GB) University of New South Wales (UNSW) Australia (AU) University of Hawaii (U.H.) United States (USA) (US) University of Alberta Canada (CA) Westmead Hospital Australia (AU) Addenbrooke's Hospital United Kingdom (GB) Ciber de Enfermedades Raras (CIBERER) Spain (ES) Stanford University United States (USA) (US) University of California Los Angeles (UCLA) United States (USA) (US) Alberta Health Services (AHS) Canada (CA) Leopold-Franzens-Universität Innsbruck / University of Innsbruck Austria (AT) Icahn School of Medicine at Mount Sinai United States (USA) (US) Hospital de la Santa Creu i Sant Pau Spain (ES) University of Nottingham United Kingdom (GB) Cedars-Sinai Medical Center United States (USA) (US) Nottingham University Hospitals United Kingdom (GB) University College London (UCL) United Kingdom (GB) University of Gothenburg / Göteborgs universitet Sweden (SE) The Daffodil Centre Australia (AU) University of São Paulo / Universidade de São Paulo (USP) Brazil (BR) Canada's Michael Smith Genome Sciences Centre Canada (CA) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) University of Utah United States (USA) (US) Uniwersytet Rzeszowski Poland (PL) University of Colorado Anschutz Medical Campus United States (USA) (US) British Columbia Cancer Agency Canada (CA) Emory University United States (USA) (US) South Carolina Department of Health and Environmental Control United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE)

How to cite

APA:

Köbel, M., Kang, E.-Y., Weir, A., Rambau, P.F., Lee, C.-H., Nelson, G.S.,... Brenton, J.D. (2023). p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study. Journal of Pathology: Clinical Research, 9(3), 208-222. https://doi.org/10.1002/cjp2.311

MLA:

Köbel, Martin, et al. "p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study." Journal of Pathology: Clinical Research 9.3 (2023): 208-222.

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