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, Josep, 1958-ca
- dc.contributor.author Font-Tello, Albaca
- dc.contributor.author Juanpere, Nuriaca
- dc.contributor.author Frances, Albertca
- dc.contributor.author Lorenzo Perez, Martaca
- dc.contributor.author Nonell Mazelon, Lara, 1972-ca
- dc.contributor.author Muga, Silvia deca
- dc.contributor.author Vázquez‐de las Heras, Ivonneca
- dc.contributor.author Cecchini Rosell, Lluísca
- dc.contributor.author Hernández, Silviaca
- dc.date.accessioned 2018-03-14T09:27:06Z
- dc.date.issued 2017
- 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.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;62:222-31. DOI: 10.1016/j.humpath.2016.12.022
- dc.identifier.doi http://dx.doi.org/10.1016/j.humpath.2016.12.022
- dc.identifier.issn 0046-8177
- dc.identifier.uri http://hdl.handle.net/10230/34095
- dc.language.iso eng
- dc.publisher Elsevierca
- dc.relation.ispartof Human Pathology. 2017 Apr;62:222-31
- dc.rights © Elsevier http://dx.doi.org/10.1016/j.humpath.2016.12.022
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.subject.keyword Bladder Cancer
- dc.subject.keyword FOXO1
- dc.subject.keyword Progression
- dc.subject.keyword Recurrence
- dc.subject.keyword p53
- 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 overexpressionca
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/acceptedVersion