Rambau, Peter FVierkant, Robert AIntermaggio, Maria PKelemen, Linda EGoodman, Marc THerpel, EstherPharoah, Paul DKommoss, StefanJimenez-Linan, MercedesKarlan, Beth YGentry-Maharaj, AleksandraMenon, UshaPolo, Susanna HernandoCandido Dos Reis, Francisco JDoherty, Jennifer AnneGayther, Simon ASharma, RaghwaLarson, Melissa CHarnett, Paul RHatfield, Emmade Andrade, Jurandyr MNelson, Gregg SSteed, HelenSchildkraut, Joellen MCarney, Micheal EHøgdall, EstridWhittemore, Alice SWidschwendter, MartinKennedy, Catherine JWang, FrancesWang, QinWang, ChenArmasu, Sebastian MDaley, FrancesCoulson, PennyJones, Micheal EAnglesio, Micheal SChow, Christinede Fazio, AnnaGarcía-Closas, MontserratBrucker, Sara YCybulski, CezaryHarris, Holly RHartkopf, Andreas DHuzarski, TomaszJensen, AllanLubiński, JanOszurek, OlegBenitez, JavierMina, FadyStaebler, AnnetteTaran, Florin AndreiPasternak, JanaTalhouk, AlineRossing, Mary AnneHendley, JoyEdwards, Robert PFereday, SianModugno, FrancesmaryNess, Roberta BSieh, WeivaEl-Bahrawy, Mona AWinham, Stacey JLester, JennyKjaer, Susanne KGronwald, JacekSinn, PeterFasching, Peter AChang-Claude, JennyMoysich, Kirsten BBowtell, David DHernandez, Brenda YLuk, HughBehrens, SabineShah, MitulJung, AudreyGhatage, PrafullAlsop, JenniferAlsop, KathrynGarcía-Donas, JesúsThompson, Pamela JSwerdlow, Anthony JKarpinskyj, ChloeCazorla-Jiménez, AliciaGarcía, María JDeen, SushaWilkens, Lynne RPalacios, JoséBerchuck, AndrewKoziak, Jennifer MBrenton, James DCook, Linda SGoode, Ellen LHuntsman, David GRamus, Susan JKöbel, Martin2018-11-222018-11-222018-10J Pathol Clin Res. (2018); 4(4):250-261.20564538http://hdl.handle.net/20.500.12105/6701We 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.engVoRhttp://creativecommons.org/licenses/by/4.0/RT-QPCRImmunocytochemistryOvaryAtribución 4.0 Internacional3006286244250-26110.1002/cjp2.1092056-4538The journal of pathology. Clinical researchopen access