p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study.
p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study.
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p53与卵巢癌生存率：一项卵巢肿瘤组织分析联盟的研究
DOI：
10.1002/cjp2.311
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发表时间：
2023-05
影响因子：
4.1
通讯作者：
Brenton, James D.
中科院分区：
文献类型：
--
作者：
Kobel, 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;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;Lubinski, Jan;Longacre, Teri A.;Lycke, Maria;Mateoiu, Constantina;McCauley, Bryan M.;McGuire, Valerie;Ney, Britta;Olawaiye, Alexander;Orsulic, Sandra;Osorio, Ana;Paz-Ares, Luis;Ramon 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, Renee T.;Garcia, Maria 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 D. P.;Schildkraut, Joellen M.;Sieh, Weiva;Staebler, Annette;Sundfeldt, Karin;Swerdlow, Anthony J.;Ramus, Susan J.;Brenton, James D.
我们的目的是使用来自卵巢肿瘤组织分析（OTTA）联盟的大型多机构队列来测试p53表达状态是否与诊断为最常见的卵巢癌组织型（高级别浆液性癌[HGSC]，类浆液性癌[EC]和透明细胞癌[CCC]）的女性的生存率相关。使用先前验证的免疫组织化学（IHC）测定法评估了来自25个参与OTTA研究的地点的组织微阵列上代表的6，678个病例的p53表达，作为TP53突变的存在和功能效应的替代物。记录了三种异常表达模式（过度表达、完全缺失和胞质）和正常（野生型）模式。通过组织型进行生存分析。p53蛋白异常表达率分别为93.4%（4,630/4,957）、11.9%（116/973）和11.5%（86/748）。在HGSC中，异常p53表达模式的总生存率没有差异。然而，在EC和CCC中，与正常p53作为参考相比，在多变量分析中，异常p53表达与诊断患有EC的女性死亡风险增加相关（风险比[HR]= 2.18，95%置信区间[CI] 1.36 - 3.47，p = 0.0011）和CCC（HR = 1.57，95% CI 1.11 - 2.22，p = 0.012）。在国际妇产科联合会I/II期EC和CCC中，异常p53也与总生存期较短相关。我们的研究提供了进一步的证据表明，通过异常替代p53 IHC模式评估的TP53突变的功能组与HGSC的生存无关。相反，我们证实异常p53 IHC是EC的一个强有力的独立预后标志物，并首次证明异常p53 IHC与CCC患者总生存期的独立预后相关性。
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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影响因子：
4.7
作者：
Koebel, Martin;Kalloger, Steve E.;Swenerton, Kenneth D.
通讯作者：
Swenerton, Kenneth D.
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1002/path.5849
发表时间：
2022-04
期刊：
The Journal of pathology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1158/1055-9965.epi-09-0880
发表时间：
2010-03
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Anderson KS;Wong J;Vitonis A;Crum CP;Sluss PM;Labaer J;Cramer D
通讯作者：
Cramer D
DOI：
10.1002/cjp2.243
发表时间：
2022-01
期刊：
The journal of pathology. Clinical research
影响因子：
--
作者：
Kang EY;Wiebe NJ;Aubrey C;Lee CH;Anglesio MS;Tilley D;Ghatage P;Nelson GS;Lee S;Köbel M
通讯作者：
Köbel M