The effect of RORa expression on the development of biological malignancy of urinary bladder cancer

Abstract

Background: Morbidity and mortality relating to urinary bladder cancer have remained largely unchanged for many years. Similarly, the five-year survival rate in this disease has not improved considerably. New developments in individualized therapy necessitate the search for novel factors that could predict the development of malignancy in UBC. In this study, we provide the first evidence that the expression of ROR alpha transcription factor influences the development of malignancy in UBC. Materials and methods: 105 patients with stage pT1-pT4 urothelial bladder carcinoma who underwent cystectomy were included in the study. 4 μm tissue samples were stained immunohistochemically with a polyclonal anti-RORa antibody. The expression of RORa by the tumor cells (TCs) was assessed by counting TCs with a cytoplasmic and/or nuclear staining for RORa per 1000 TCs. The association between the extent of RORa expression and non-classic differentiation, tumor advancement (pT), grade (G) and regional lymph node spread was analyzed. Results: The cytoplasmic expression of RORa was detected in near all analyzed tumor samples (104/105). The extent of RORa expression was significantly higher in tumors which were more malignant with more propensity for non-classic differentiation and lymph node metastasis. We noted a lower percentage of TCs expressing RORa in poorly differentiated tumors (G3), compared to tumors moderately and higher differentiated (G1/G2). Conclusions: Our results suggest that RORa may play a significant role in the progression of urinary bladder cancer. RORa has a broad spectrum of regulatory activity relating to cell and tissue differentiation the mechanism of which is not fully understood. This study represents another step in the process of understanding the mechanisms of RORa regulation and highlights its potential role as a therapeutic target in urothelial bladder cancer.