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000141417 0247_ $$2doi$$a10.1002/cjp2.109
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000141417 0247_ $$2pmc$$apmc:PMC6174617
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000141417 037__ $$aDKFZ-2018-01923
000141417 041__ $$aeng
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000141417 1001_ $$aRambau, Peter F$$b0
000141417 245__ $$aAssociation of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study.
000141417 260__ $$aChichester$$bWiley$$c2018
000141417 3367_ $$2DRIVER$$aarticle
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000141417 520__ $$aWe aimed to validate the prognostic association of p16 expression in ovarian high-grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical-grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis-associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47-2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30-2.75, p = 0.004), while absence was associated with shorter OS in low-grade serous carcinomas (HR: 2.95, 95% CI 1.61-5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype-specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low-grade serous carcinoma justifies CDK4 inhibition.
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000141417 7001_ $$aVierkant, Robert A$$b1
000141417 7001_ $$aIntermaggio, Maria P$$b2
000141417 7001_ $$aKelemen, Linda E$$b3
000141417 7001_ $$aGoodman, Marc T$$b4
000141417 7001_ $$aHerpel, Esther$$b5
000141417 7001_ $$aPharoah, Paul D$$b6
000141417 7001_ $$aKommoss, Stefan$$b7
000141417 7001_ $$aJimenez-Linan, Mercedes$$b8
000141417 7001_ $$aKarlan, Beth Y$$b9
000141417 7001_ $$aGentry-Maharaj, Aleksandra$$b10
000141417 7001_ $$aMenon, Usha$$b11
000141417 7001_ $$aPolo, Susanna Hernando$$b12
000141417 7001_ $$aCandido Dos Reis, Francisco J$$b13
000141417 7001_ $$aDoherty, Jennifer Anne$$b14
000141417 7001_ $$aGayther, Simon A$$b15
000141417 7001_ $$aSharma, Raghwa$$b16
000141417 7001_ $$aLarson, Melissa C$$b17
000141417 7001_ $$aHarnett, Paul R$$b18
000141417 7001_ $$aHatfield, Emma$$b19
000141417 7001_ $$ade Andrade, Jurandyr M$$b20
000141417 7001_ $$aNelson, Gregg S$$b21
000141417 7001_ $$aSteed, Helen$$b22
000141417 7001_ $$aSchildkraut, Joellen M$$b23
000141417 7001_ $$aCarney, Micheal E$$b24
000141417 7001_ $$aHøgdall, Estrid$$b25
000141417 7001_ $$aWhittemore, Alice S$$b26
000141417 7001_ $$aWidschwendter, Martin$$b27
000141417 7001_ $$aKennedy, Catherine J$$b28
000141417 7001_ $$aWang, Frances$$b29
000141417 7001_ $$aWang, Qin$$b30
000141417 7001_ $$aWang, Chen$$b31
000141417 7001_ $$aArmasu, Sebastian M$$b32
000141417 7001_ $$aDaley, Frances$$b33
000141417 7001_ $$aCoulson, Penny$$b34
000141417 7001_ $$aJones, Micheal E$$b35
000141417 7001_ $$aAnglesio, Micheal S$$b36
000141417 7001_ $$aChow, Christine$$b37
000141417 7001_ $$ade Fazio, Anna$$b38
000141417 7001_ $$aGarcía-Closas, Montserrat$$b39
000141417 7001_ $$aBrucker, Sara Y$$b40
000141417 7001_ $$aCybulski, Cezary$$b41
000141417 7001_ $$aHarris, Holly R$$b42
000141417 7001_ $$aHartkopf, Andreas D$$b43
000141417 7001_ $$aHuzarski, Tomasz$$b44
000141417 7001_ $$aJensen, Allan$$b45
000141417 7001_ $$aLubiński, Jan$$b46
000141417 7001_ $$aOszurek, Oleg$$b47
000141417 7001_ $$aBenitez, Javier$$b48
000141417 7001_ $$aMina, Fady$$b49
000141417 7001_ $$aStaebler, Annette$$b50
000141417 7001_ $$aTaran, Florin Andrei$$b51
000141417 7001_ $$aPasternak, Jana$$b52
000141417 7001_ $$aTalhouk, Aline$$b53
000141417 7001_ $$aRossing, Mary Anne$$b54
000141417 7001_ $$aHendley, Joy$$b55
000141417 7001_ $$aGroup, AOCS$$b56$$eCollaboration Author
000141417 7001_ $$aEdwards, Robert P$$b57
000141417 7001_ $$aFereday, Sian$$b58
000141417 7001_ $$aModugno, Francesmary$$b59
000141417 7001_ $$aNess, Roberta B$$b60
000141417 7001_ $$aSieh, Weiva$$b61
000141417 7001_ $$aEl-Bahrawy, Mona A$$b62
000141417 7001_ $$aWinham, Stacey J$$b63
000141417 7001_ $$aLester, Jenny$$b64
000141417 7001_ $$aKjaer, Susanne K$$b65
000141417 7001_ $$aGronwald, Jacek$$b66
000141417 7001_ $$aSinn, Peter$$b67
000141417 7001_ $$aFasching, Peter A$$b68
000141417 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b69$$udkfz
000141417 7001_ $$aMoysich, Kirsten B$$b70
000141417 7001_ $$aBowtell, David D$$b71
000141417 7001_ $$aHernandez, Brenda Y$$b72
000141417 7001_ $$aLuk, Hugh$$b73
000141417 7001_ $$0P:(DE-He78)6b04712f3afe72044d496a25505cb1ea$$aBehrens, Sabine$$b74$$udkfz
000141417 7001_ $$aShah, Mitul$$b75
000141417 7001_ $$aJung, Audrey$$b76
000141417 7001_ $$aGhatage, Prafull$$b77
000141417 7001_ $$aAlsop, Jennifer$$b78
000141417 7001_ $$aAlsop, Kathryn$$b79
000141417 7001_ $$aGarcía-Donas, Jesús$$b80
000141417 7001_ $$aThompson, Pamela J$$b81
000141417 7001_ $$aSwerdlow, Anthony J$$b82
000141417 7001_ $$aKarpinskyj, Chloe$$b83
000141417 7001_ $$aCazorla-Jiménez, Alicia$$b84
000141417 7001_ $$aGarcía, María J$$b85
000141417 7001_ $$aDeen, Susha$$b86
000141417 7001_ $$aWilkens, Lynne R$$b87
000141417 7001_ $$aPalacios, José$$b88
000141417 7001_ $$aBerchuck, Andrew$$b89
000141417 7001_ $$aKoziak, Jennifer M$$b90
000141417 7001_ $$aBrenton, James D$$b91
000141417 7001_ $$aCook, Linda S$$b92
000141417 7001_ $$aGoode, Ellen L$$b93
000141417 7001_ $$aHuntsman, David G$$b94
000141417 7001_ $$aRamus, Susan J$$b95
000141417 7001_ $$00000-0002-6615-2037$$aKöbel, Martin$$b96
000141417 773__ $$0PERI:(DE-600)2814357-7$$a10.1002/cjp2.109$$gVol. 4, no. 4, p. 250 - 261$$n4$$p250 - 261$$tThe journal of pathology: clinical research$$v4$$x2056-4538$$y2018
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