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

Publication date: Available online 11 January 2017
Source:Human Pathology
Author(s): Josep Lloreta, Alba Font-Tello, Núria Juanpere, Albert Frances, Marta Lorenzo, Lara Nonell, Silvia de Muga, Ivonne Vázquez, Lluís Cecchini, Silvia Hernández-Llodrà
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 downregulation/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 (HR=3.18, 95% CI 1.19–8.48 P=.02), but this association was even stronger if having any alteration in any of the two genes was considered (HR=3.51, 95% CI 1.34–9.21 P=.01). Having both FOXO1 downregulation 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 two genes was associated with progression in low grade (P=.005) and pTa (P=.006) tumors. Finally, the combined FOXO1 downregulation/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.



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