Abstract
The transcription factor forkhead box O1 (FOXO1) can be inactivated via its phosphorylation, resulting in suppression of apoptosis. Using immunohistochemistry, the expression of a phosphorylated form of FOXO1 was assessed in upper urinary tract urothelial carcinoma (UUTUC) specimens. Overall, phospho-FOXO1 (p-FOXO1) was immunoreactive in all 99 UUTUC specimens [12 (12.1%) weak (1+), 46 (46.5%) moderate (2+) and 41 (41.4%) strong (3+)], which was significantly (P=0.018) increased, compared with benign urothelium specimens [77/82 (93.9%): 18 (22.0%) 1+, 41 (50.0%) 2+ and 18 (22.0%) 3+]. Muscle invasion (P=0.031) and lymphovascular invasion (P=0.025) were observed more frequently in p-FOXO1(2+/3+) tumor samples compared with p-FOXO1(1+) tumor samples. No statistically significant associations between p-FOXO1 expression and tumor grade or presence of concurrent carcinoma in situ, hydronephrosis or lymph node metastasis were observed. Furthermore, the levels of p-FOXO1 and estrogen receptor-β expression were significantly (P<0.05) correlated in UUTUC samples [correlation coefficient (CC)=0.244], particularly in tumor samples from male patients (CC=0.330). Additionally, patients with p-FOXO1(3+) tumors had a significantly increased risk of cancer-specific mortality (P=0.043), compared with those with p-FOXO1(1+/2+) tumors. Multivariate analysis further demonstrated a notable, albeit not significant, association between p-FOXO1 expression and cancer-specific survival (hazard ratio=2.204; P=0.053). These findings indicate that FOXO1 is inactivated in UUTUC specimens and p-FOXO1 overexpression may serve as a predictor of poor patient outcomes.