TY  - JOUR
SN  - 2056-4538
SP  - 250
KW  - RT-QPCR
KW  -  immunocytochemistry
KW  -  ovary
IS  - 4
JF  - The Journal of Pathology: Clinical Research
AV  - public
TI  - Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study
Y1  - 2018/10//
N1  - © 2018 The Authors.

This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
ID  - discovery10054143
A1  - Rambau, PF
A1  - Vierkant, RA
A1  - Intermaggio, MP
A1  - Kelemen, LE
A1  - Goodman, MT
A1  - Herpel, E
A1  - Pharoah, PD
A1  - Kommoss, S
A1  - Jimenez-Linan, M
A1  - Karlan, BY
A1  - Gentry-Maharaj, A
A1  - Menon, U
A1  - Polo, SH
A1  - Candido Dos Reis, FJ
A1  - Doherty, JA
A1  - Gayther, SA
A1  - Sharma, R
A1  - Larson, MC
A1  - Harnett, PR
A1  - Hatfield, E
A1  - de Andrade, JM
A1  - Nelson, GS
A1  - Steed, H
A1  - Schildkraut, JM
A1  - Carney, ME
A1  - Høgdall, E
A1  - Whittemore, AS
A1  - Widschwendter, M
A1  - Kennedy, CJ
A1  - Wang, F
A1  - Wang, Q
A1  - Wang, C
A1  - Armasu, SM
A1  - Daley, F
A1  - Coulson, P
A1  - Jones, ME
A1  - Anglesio, MS
A1  - Chow, C
A1  - de Fazio, A
A1  - García-Closas, M
A1  - Brucker, SY
A1  - Cybulski, C
A1  - Harris, HR
A1  - Hartkopf, AD
A1  - Huzarski, T
A1  - Jensen, A
A1  - Lubi?ski, J
A1  - Oszurek, O
A1  - Benitez, J
A1  - Mina, F
A1  - Staebler, A
A1  - Taran, FA
A1  - Pasternak, J
A1  - Talhouk, A
A1  - Rossing, MA
A1  - Hendley, J
A1  - AOCS Group, .
A1  - Edwards, RP
A1  - Fereday, S
A1  - Modugno, F
A1  - Ness, RB
A1  - Sieh, W
A1  - El-Bahrawy, MA
A1  - Winham, SJ
A1  - Lester, J
A1  - Kjaer, SK
A1  - Gronwald, J
A1  - Sinn, P
A1  - Fasching, PA
A1  - Chang-Claude, J
A1  - Moysich, KB
A1  - Bowtell, DD
A1  - Hernandez, BY
A1  - Luk, H
A1  - Behrens, S
A1  - Shah, M
A1  - Jung, A
A1  - Ghatage, P
A1  - Alsop, J
A1  - Alsop, K
A1  - García-Donas, J
A1  - Thompson, PJ
A1  - Swerdlow, AJ
A1  - Karpinskyj, C
A1  - Cazorla-Jiménez, A
A1  - García, MJ
A1  - Deen, S
A1  - Wilkens, LR
A1  - Palacios, J
A1  - Berchuck, A
A1  - Koziak, JM
A1  - Brenton, JD
A1  - Cook, LS
A1  - Goode, EL
A1  - Huntsman, DG
A1  - Ramus, SJ
A1  - Köbel, M
VL  - 4
UR  - https://doi.org/10.1002/cjp2.109
N2  - 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.
EP  - 261
ER  -