p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study
Authors: Köbel Martin , Kang Eun‐Young , Weir Ashley , Rambau Peter F , Lee Cheng‐Han , Nelson Gregg S , Ghatage Prafull , Meagher Nicola S , Riggan Marjorie J , Alsop Jennifer , Anglesio Michael S , Beckmann Matthias W , Bisinotto Christiani , Boisen Michelle , Boros Jessica , Brand Alison H , Brooks‐Wilson Angela , Carney Michael E , Coulson Penny , Courtney‐Brooks Madeleine , Cushing‐Haugen Kara L , Cybulski Cezary , Deen Suha , El‐Bahrawy Mona A , Elishaev Esther , Erber Ramona , Fereday Sian ,   AOCS Group, Fischer Anna , Gayther Simon A , Barquin‐Garcia Arantzazu , Gentry‐Maharaj Aleksandra , Gilks C Blake , Gronwald Helena , Grube Marcel , Harnett Paul R , Harris Holly R , Hartkopf Andreas D , Hartmann Arndt , Hein Alexander , Hendley Joy , Hernandez Brenda Y , Huang Yajue , Jakubowska Anna , Jimenez‐Linan Mercedes , Jones Michael E , Kennedy Catherine J , Kluz Tomasz , Koziak Jennifer M , Lesnock Jaime , Lester Jenny , Lubiński Jan , Longacre Teri A , Lycke Maria , Mateoiu Constantina , McCauley Bryan M , McGuire Valerie , Ney Britta , Olawaiye Alexander , Orsulic Sandra , Osorio Ana , Paz‐Ares Luis , Ramón y Cajal Teresa , Rothstein Joseph H , Ruebner Matthias , Schoemaker Minouk J , Shah Mitul , Sharma Raghwa , Sherman Mark E , Shvetsov Yurii B , Singh Naveena , Steed Helen , Storr Sarah J , Talhouk Aline , Traficante Nadia , Wang Chen , Whittemore Alice S , Widschwendter Martin , Wilkens Lynne R , Winham Stacey J , Benitez Javier , Berchuck Andrew , Bowtell David D , Candido dos Reis Francisco J , Campbell Ian , Cook Linda S , DeFazio Anna , Doherty Jennifer A , Fasching Peter A , Fortner Renée T , García María J , Goodman Marc T , Goode Ellen L , Gronwald Jacek , Huntsman David G , Karlan Beth Y , Kelemen Linda E , Kommoss Stefan , Le Nhu D , Martin Stewart G , Menon Usha , Modugno Francesmary , Pharoah Paul DP , Schildkraut Joellen M , Sieh Weiva , Staebler Annette , Sundfeldt Karin , Swerdlow Anthony J , Ramus Susan J , Brenton James D 
Published: March 2023

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.