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oai:repisalud.isciii.es:20.500.12105/67012025-03-24T14:27:55Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud author Rambau, Peter F author Vierkant, Robert A author Intermaggio, Maria P author Kelemen, Linda E author Goodman, Marc T author Herpel, Esther author Pharoah, Paul D author Kommoss, Stefan author Jimenez-Linan, Mercedes author Karlan, Beth Y author Gentry-Maharaj, Aleksandra author Menon, Usha author Polo, Susanna Hernando author Candido Dos Reis, Francisco J author Doherty, Jennifer Anne author Gayther, Simon A author Sharma, Raghwa author Larson, Melissa C author Harnett, Paul R author Hatfield, Emma author de Andrade, Jurandyr M author Nelson, Gregg S author Steed, Helen author Schildkraut, Joellen M author Carney, Micheal E author Høgdall, Estrid author Whittemore, Alice S author Widschwendter, Martin author Kennedy, Catherine J author Wang, Frances author Wang, Qin author Wang, Chen author Armasu, Sebastian M author Daley, Frances author Coulson, Penny author Jones, Micheal E author Anglesio, Micheal S author Chow, Christine author de Fazio, Anna author García-Closas, Montserrat author Brucker, Sara Y author Cybulski, Cezary author Harris, Holly R author Hartkopf, Andreas D author Huzarski, Tomasz author Jensen, Allan author Lubiński, Jan author Oszurek, Oleg author Benitez, Javier author Mina, Fady author Staebler, Annette author Taran, Florin Andrei author Pasternak, Jana author Talhouk, Aline author Rossing, Mary Anne author Hendley, Joy author Edwards, Robert P author Fereday, Sian author Modugno, Francesmary author Ness, Roberta B author Sieh, Weiva author El-Bahrawy, Mona A author Winham, Stacey J author Lester, Jenny author Kjaer, Susanne K author Gronwald, Jacek author Sinn, Peter author Fasching, Peter A author Chang-Claude, Jenny author Moysich, Kirsten B author Bowtell, David D author Hernandez, Brenda Y author Luk, Hugh author Behrens, Sabine author Shah, Mitul author Jung, Audrey author Ghatage, Prafull author Alsop, Jennifer author Alsop, Kathryn author García-Donas, Jesús author Thompson, Pamela J author Swerdlow, Anthony J author Karpinskyj, Chloe author Cazorla-Jiménez, Alicia author García, María J author Deen, Susha author Wilkens, Lynne R author Palacios, José author Berchuck, Andrew author Koziak, Jennifer M author Brenton, James D author Cook, Linda S author Goode, Ellen L author Huntsman, David G author Ramus, Susan J author Köbel, Martin funder Ovarian Cancer Australia funder Peter MacCallum Foundation funder NIHR - Royal Marsden Biomedical Research Centre (Reino Unido) funder National Center for Tumor Diseases (Alemania) funder Cancer Council Victoria (Australia) funder Cancer Council New South Wales (Australia) funder Cancer Council Queensland (Australia) funder Cancer Council Western Australia (Australia) funder Cancer Council Tasmania (Australia) funder Ministerio de Economía y Competitividad (España) funder National Center for Advancing Translational Sciences (Estados Unidos) funder Danish Cancer Foundation funder NIH - National Cancer Institute (NCI) (Estados Unidos) funder Instituto de Salud Carlos III 2018-11-22T09:17:32Z 2018-11-22T09:17:32Z 2018-10 J Pathol Clin Res. (2018); 4(4):250-261. 10.1002/cjp2.109 2056-4538 20564538 The journal of pathology. Clinical research 30062862 http://hdl.handle.net/20.500.12105/6701 We aimed to validate the prognostic association of p16 expression in ovarian high-grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical-grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis-associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47-2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30-2.75, p = 0.004), while absence was associated with shorter OS in low-grade serous carcinomas (HR: 2.95, 95% CI 1.61-5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype-specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low-grade serous carcinoma justifies CDK4 inhibition. eng RT-QPCR Immunocytochemistry Ovary Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study research article 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 URL https://repisalud.isciii.es/bitstreams/2e53d2ea-d374-48e1-90b3-9adb6ad4b504/download File MD5 89e1aa27ac9644a537924a4055bac9e2 408614 application/pdf Associationof16expressionwithprognosis_2018.pdf URL https://repisalud.isciii.es/bitstreams/d5e8fc55-c6b1-4efb-a2fb-c72d7e786997/download File MD5 4f2bf98043a627030b909aba04b08bf1 59099 text/plain Associationof16expressionwithprognosis_2018.pdf.txt