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FOXO1 down-regulation is associated with worse outcome in bladder cancer and adds significant prognostic information to p53 overexpression

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dc.contributor.author Lloreta Trull, Josep, 1958-
dc.contributor.author Font-Tello, Alba
dc.contributor.author Juanpere, Nuria
dc.contributor.author Frances, Albert
dc.contributor.author Lorenzo Perez, Marta
dc.contributor.author Nonell Mazelón, Lara
dc.contributor.author Muga, Silvia de
dc.contributor.author Vázquez‐de las Heras, Ivonne
dc.contributor.author Cecchini Rosell, Lluís
dc.contributor.author Hernández, Silvia
dc.date.accessioned 2018-03-14T09:27:06Z
dc.date.issued 2017
dc.identifier.citation Lloreta J, Font-Tello A, Juanpere N, Frances A, Lorenzo M, Nonell L et al. FOXO1 down-regulation is associated with worse outcome in bladder cancer and adds significant prognostic information to p53 overexpression. Hum Pathol. 2017 Apr;62:222-231. DOI: 10.1016/j.humpath.2016.12.022
dc.identifier.issn 0046-8177
dc.identifier.uri http://hdl.handle.net/10230/34095
dc.description.abstract Nuclear FOXOs mediate cell cycle arrest and promote apoptosis. FOXOs and p53 could have similar effects as tumor suppressor genes. In spite of extensive literature, little is known about the role of FOXO1 and its relationship with p53 status in bladder cancer. Expression of FOXO1 and p53 were analyzed by immunohistochemistry in 162 urothelial carcinomas (UC). Decreased FOXO1 expression, p53 overexpression and the combination FOXO1 down-regulation/p53 overexpression were strongly associated with high grade (P=.030; P=.017; P=.004, respectively), high stage (P=.0001; P<.0001; P<.0001, respectively) or both (P=.0004; P<.0001; P<.0001, respectively). In the overall series of cases, p53 overexpression was associated with tumor progression (hazard ratio [HR]=3.18, 95% confidence interval [CI] 1.19-8.48, P=.02), but this association was even stronger if having any alteration in any of the 2 genes was considered (HR=3.51, 95% CI 1.34-9.21, P=.01). Having both FOXO1 down-regulation and p53 overexpression was associated with disease recurrence (HR=2.75, 95% CI 1.06-7.13, P=.03). In the analysis of the different subgroups, having any alteration in any of the 2 genes was associated with progression in low-grade (P=.005) and pTa (P=.006) tumors. Finally, the combined FOXO1 down-regulation/p53 overexpression was associated with disease recurrence specifically in high-grade (P=.04) and in pT1 stage tumors (P=.007). Adding FOXO1 expression to the immunohistochemical analysis of p53 can provide relevant prognostic information on progression and recurrence of bladder cancer. It may be particularly informative on the risk of progression in the more indolent and on the risk of recurrence in the more aggressive tumors.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.rights © Elsevier http://dx.doi.org/10.1016/j.humpath.2016.12.022
dc.subject.other Bufeta -- Càncer
dc.title FOXO1 down-regulation is associated with worse outcome in bladder cancer and adds significant prognostic information to p53 overexpression
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.humpath.2016.12.022
dc.subject.keyword Bladder Cancer
dc.subject.keyword FOXO1
dc.subject.keyword Progression
dc.subject.keyword Recurrence
dc.subject.keyword p53
dc.rights.accessRights info:eu-repo/semantics/embargoedAccess
dc.type.version info:eu-repo/semantics/acceptedVersion
dc.embargo.liftdate 2018-04-01
dc.date.embargoEnd info:eu-repo/date/embargoEnd/2018-04-01


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