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@ARTICLE{Rambau:141417,
author = {P. F. Rambau and R. A. Vierkant and M. P. Intermaggio and
L. E. Kelemen and M. T. Goodman and E. Herpel and P. D.
Pharoah and S. Kommoss and M. Jimenez-Linan and B. Y. Karlan
and A. Gentry-Maharaj and U. Menon and S. H. Polo and F. J.
Candido Dos Reis and J. A. Doherty and S. A. Gayther and R.
Sharma and M. C. Larson and P. R. Harnett and E. Hatfield
and J. M. de Andrade and G. S. Nelson and H. Steed and J. M.
Schildkraut and M. E. Carney and E. Høgdall and A. S.
Whittemore and M. Widschwendter and C. J. Kennedy and F.
Wang and Q. Wang and C. Wang and S. M. Armasu and F. Daley
and P. Coulson and M. E. Jones and M. S. Anglesio and C.
Chow and A. de Fazio and M. García-Closas and S. Y. Brucker
and C. Cybulski and H. R. Harris and A. D. Hartkopf and T.
Huzarski and A. Jensen and J. Lubiński and O. Oszurek and
J. Benitez and F. Mina and A. Staebler and F. A. Taran and
J. Pasternak and A. Talhouk and M. A. Rossing and J. Hendley
and R. P. Edwards and S. Fereday and F. Modugno and R. B.
Ness and W. Sieh and M. A. El-Bahrawy and S. J. Winham and
J. Lester and S. K. Kjaer and J. Gronwald and P. Sinn and P.
A. Fasching and J. Chang-Claude$^*$ and K. B. Moysich and D.
D. Bowtell and B. Y. Hernandez and H. Luk and S. Behrens$^*$
and M. Shah and A. Jung and P. Ghatage and J. Alsop and K.
Alsop and J. García-Donas and P. J. Thompson and A. J.
Swerdlow and C. Karpinskyj and A. Cazorla-Jiménez and M. J.
García and S. Deen and L. R. Wilkens and J. Palacios and A.
Berchuck and J. M. Koziak and J. D. Brenton and L. S. Cook
and E. L. Goode and D. G. Huntsman and S. J. Ramus and M.
Köbel},
collaboration = {A. Group},
title = {{A}ssociation of p16 expression with prognosis varies
across ovarian carcinoma histotypes: an {O}varian {T}umor
{T}issue {A}nalysis consortium study.},
journal = {The journal of pathology: clinical research},
volume = {4},
number = {4},
issn = {2056-4538},
address = {Chichester},
publisher = {Wiley},
reportid = {DKFZ-2018-01923},
pages = {250 - 261},
year = {2018},
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.},
cin = {C020},
ddc = {610},
cid = {I:(DE-He78)C020-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30062862},
pmc = {pmc:PMC6174617},
doi = {10.1002/cjp2.109},
url = {https://inrepo02.dkfz.de/record/141417},
}