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Title: Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study.
Rambau, Peter F
Vierkant, Robert A
Intermaggio, Maria P
Kelemen, Linda E
Goodman, Marc T
Herpel, Esther
Pharoah, Paul D
Kommoss, Stefan
Jimenez-Linan, Mercedes
Karlan, Beth Y
Gentry-Maharaj, Aleksandra
Menon, Usha
Polo, Susanna Hernando
Candido Dos Reis, Francisco J
Doherty, Jennifer Anne
Gayther, Simon A
Sharma, Raghwa
Larson, Melissa C
Harnett, Paul R
Hatfield, Emma
de Andrade, Jurandyr M
Nelson, Gregg S
Steed, Helen
Schildkraut, Joellen M
Carney, Micheal E
Høgdall, Estrid
Whittemore, Alice S
Widschwendter, Martin
Kennedy, Catherine J
Wang, Frances
Wang, Qin
Wang, Chen
Armasu, Sebastian M
Daley, Frances
Coulson, Penny
Jones, Micheal E
Anglesio, Micheal S
Chow, Christine
de Fazio, Anna
García-Closas, Montserrat
Brucker, Sara Y
Cybulski, Cezary
Harris, Holly R
Hartkopf, Andreas D
Huzarski, Tomasz
Jensen, Allan
Lubiński, Jan
Oszurek, Oleg
Benitez, Javier
Mina, Fady
Staebler, Annette
Taran, Florin Andrei
Pasternak, Jana
Talhouk, Aline
Rossing, Mary Anne
Hendley, Joy
Edwards, Robert P
Fereday, Sian
Modugno, Francesmary
Ness, Roberta B
Sieh, Weiva
El-Bahrawy, Mona A
Winham, Stacey J
Lester, Jenny
Kjaer, Susanne K
Gronwald, Jacek
Sinn, Peter
Fasching, Peter A
Chang-Claude, Jenny
Moysich, Kirsten B
Bowtell, David D
Hernandez, Brenda Y
Luk, Hugh
Behrens, Sabine
Shah, Mitul
Jung, Audrey
Ghatage, Prafull
Alsop, Jennifer
Alsop, Kathryn
García-Donas, Jesús
Thompson, Pamela J
Swerdlow, Anthony J
Karpinskyj, Chloe
Cazorla-Jiménez, Alicia
García, María J
Deen, Susha
Wilkens, Lynne R
Palacios, José
Berchuck, Andrew
Koziak, Jennifer M
Brenton, James D
Cook, Linda S
Goode, Ellen L
Huntsman, David G
Ramus, Susan J
Köbel, Martin
Issue Date: Oct-2018
Citation: J Pathol Clin Res.2018 Oct;(4)4:250-261
Abstract: 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.
PMID: 30062862
Rights: openAccess
Appears in Collections:Fundaciones e Institutos de Investigación > IIS H. U. Ramón y Cajal > Artículos

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