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oai:repisalud.isciii.es:20.500.12105/189002024-11-29T20:41:29Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Weir, Ashley author Kang, Eun-Young author Meagher, Nicola S author Nelson, Gregg S author Ghatage, Prafull author Lee, Cheng-Han author Riggan, Marjorie J author Gentry-Maharaj, Aleksandra author Ryan, Andy author Singh, Naveena author Widschwendter, Martin author Alsop, Jennifer author Anglesio, Michael S author Beckmann, Matthias W author Berger, Jessica author Bisinotto, Christiani author Boros, Jessica author Brand, Alison H author Brenton, James D author Brooks-Wilson, Angela author Carney, Michael E author Cunningham, Julie M author Cushing-Haugen, Kara L author Cybulski, Cezary author Elishaev, Esther author Erber, Ramona author Fereday, Sian author Fischer, Anna author Paz Ares, Luis Gonzaga author Gayarre, Javier author Gilks, Blake C author Grube, Marcel author Harnett, Paul R author Harris, Holly R author Hartmann, Arndt author Hein, Alexander author Hendley, Joy author Hernandez, Brenda Y author Heublein, Sabine author Huang, Yajue author Huzarski, Tomasz author Jakubowska, Anna author Jimenez-Linan, Mercedes author Kennedy, Catherine J author Kommoss, Felix K F author Koziak, Jennifer M author Kraemer, Bernhard author Le, Nhu D author Lesnock, Jaime author Lester, Jenny author Lubiński, Jan author Menkiszak, Janusz author Ney, Britta author Olawaiye, Alexander author Orsulic, Sandra author Osorio, Ana author Robles-Díaz, Luis author Ruebner, Matthias author Shah, Mitul author Sharma, Raghwa author Shvetsov, Yurii B author Steed, Helen author Talhouk, Aline author Taylor, Sarah E author Traficante, Nadia author Vierkant, Robert A author Wang, Chen author Wilkens, Lynne R author Winham, Stacey J author Benitez, Javier author Berchuck, Andrew author Bowtell, David D author Candido Dos Reis, Francisco J author Cook, Linda S author DeFazio, Anna author Doherty, Jennifer A author Fasching, Peter A author García, María J author Goode, Ellen L author Goodman, Marc T author Gronwald, Jacek author Huntsman, David G author Karlan, Beth Y author Kommoss, Stefan author Modugno, Francesmary author Schildkraut, Joellen M author Sinn, Hans-Peter author Staebler, Annette author Kelemen, Linda E author Ford, Caroline E author Menon, Usha author Pharoah, Paul D P author Köbel, Martin author Ramus, Susan J author 2023-01 BACKGROUND Recently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC. METHODS Two prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent immunohistochemical staining and scoring, then univariate and multivariate survival analysis. RESULTS Consistent with mRNA, FOXJ1 protein expression exhibited a linear, increasing association with improved overall survival in HGSC patients. Women with >50% expression had the most favourable outcomes (HR = 0.78, 95% CI 0.67-0.91, p < 0.0001). GMNN protein expression was not significantly associated with overall HSGC patient survival. However, HGSCs with >35% GMNN expression showed a trend for better outcomes, though this was not significant. CONCLUSION We provide foundational evidence for the prognostic value of FOXJ1 in HGSC, validating the prior mRNA-based prognostic association by immunohistochemistry. Br J Cancer . 2023;128(1):137-147 10.1038/s41416-022-02014-y 1532-1827 British journal of cancer 36323878 http://hdl.handle.net/20.500.12105/18900 Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study.