Journal Article

DKFZ-2023-00586

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study.

Köbel, M. ; Kang, E.-Y. ; Weir, A. ; Rambau, P. F. ; Lee, C.-H. ; Nelson, G. S. ; Ghatage, P. ; Meagher, N. S. ; Riggan, M. J. ; Alsop, J. ; Anglesio, M. S. ; Beckmann, M. W. ; Bisinotto, C. ; Boisen, M. ; Boros, J. ; Brand, A. H. ; Brooks-Wilson, A. ; Carney, M. E. ; Coulson, P. ; Courtney-Brooks, M. ; Cushing-Haugen, K. L. ; Cybulski, C. ; Deen, S. ; El-Bahrawy, M. A. ; Elishaev, E. ; Erber, R. ; Fereday, S. ; Group, A. (Collaboration Author) ; Fischer, A. ; Gayther, S. A. ; Barquin-Garcia, A. ; Gentry-Maharaj, A. ; Gilks, C. B. ; Gronwald, H. ; Grube, M. ; Harnett, P. R. ; Harris, H. R. ; Hartkopf, A. D. ; Hartmann, A. ; Hein, A. ; Hendley, J. ; Hernandez, B. Y. ; Huang, Y. ; Jakubowska, A. ; Jimenez-Linan, M. ; Jones, M. E. ; Kennedy, C. J. ; Kluz, T. ; Koziak, J. M. ; Lesnock, J. ; Lester, J. ; Lubiński, J. ; Longacre, T. A. ; Lycke, M. ; Mateoiu, C. ; McCauley, B. M. ; McGuire, V. ; Ney, B. ; Olawaiye, A. ; Orsulic, S. ; Osorio, A. ; Paz-Ares, L. ; Ramón Y Cajal, T. ; Rothstein, J. H. ; Ruebner, M. ; Schoemaker, M. J. ; Shah, M. ; Sharma, R. ; Sherman, M. E. ; Shvetsov, Y. B. ; Singh, N. ; Steed, H. ; Storr, S. J. ; Talhouk, A. ; Traficante, N. ; Wang, C. ; Whittemore, A. S. ; Widschwendter, M. ; Wilkens, L. R. ; Winham, S. J. ; Benitez, J. ; Berchuck, A. ; Bowtell, D. D. ; Candido Dos Reis, F. J. ; Campbell, I. ; Cook, L. S. ; DeFazio, A. ; Doherty, J. A. ; Fasching, P. A. ; Fortner, R. T.DKFZ* ; García, M. J. ; Goodman, M. T. ; Goode, E. L. ; Gronwald, J. ; Huntsman, D. G. ; Karlan, B. Y. ; Kelemen, L. E. ; Kommoss, S. ; Le, N. D. ; Martin, S. G. ; Menon, U. ; Modugno, F. ; Pharoah, P. D. ; Schildkraut, J. M. ; Sieh, W. ; Staebler, A. ; Sundfeldt, K. ; Swerdlow, A. J. ; Ramus, S. J. ; Brenton, J. D.

2023
Wiley Chichester

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Please use a persistent id in citations: 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.

Keyword(s): TP53 ; clear cell ; endometrioid ; high-grade serous carcinoma ; ovarian cancer ; p53 ; prognosis

Note: 2023 May;9(3):208-222

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2023

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