High Coexpression of Runt-related Transcription Factor 2 (RUNX2) and p53 Independently Predicts Early Tumor Recurrence in Bladder Urothelial Carcinoma Patients

Conventional prognostic factors for bladder cancer are inadequate to predict tumor recurrence and/or progression successfully; thus, the identification of adjunctive novel prognostic biomarkers is of paramount importance. In this study, the immunohistochemical expression patterns and clinical significance of RUNX2, WWOX, and p53 were investigated in a tissue microarray of 87 primary urothelial carcinomas and 17 control cases. We found that RUNX2, WWOX, and p53 were significantly correlated and overexpressed in urothelial carcinoma cases compared with the control group. RUNX2 and p53 were significantly upregulated in association with high-grade, nonpapillary pattern, and bilharziasis. Muscle-invasive tumors significantly overexpressed RUNX2. WWOX overexpression was significantly associated with high-grade tumors and inversely correlated with age. In a bivariate analysis, the risk of early tumor recurrence and progression was significantly associated with RUNX2 and p53 overexpression and bilharziasis. A multivariate Cox regression analysis proved that RUNX2 and p53 were independent predictors of early tumor recurrence. The ROC curve analysis showed that combined RUNX2 and p53 high expression (scores > 3 and > 5, respectively) had the highest accuracy (73.6%) for the prediction of early tumor recurrence. We conclude that RUNX2 and p53 might be functionally related and are likely involved in bladder tumor carcinogenesis and aggressiveness, which provides a new perspective for targeted therapy. RUNX2 and p53 independently predict early tumor recurrence in bladder carcinoma patients, with the highest prediction accuracy being achieved on their combined high expression. The role of WWOX in bladder urothelial carcinoma and its relationship with RUNX2 and p53 remains unclear and warrants further investigation.