Human DNA topoisomerase-IIα expression as a prognostic factor for transitional cell carcinoma of the urinary bladder

OBJECTIVE: To investigate the immunohistochemical expression of topoisomerase II-α (TII-α, a nuclear enzyme, the expression of which increases rapidly at the end of the S to G2/M phase and declines when mitosis ends) in bladder urothelial neoplasms (transitional cell carcinoma), and its correlation with grade, stage and survival. PATIENTS AND METHODS: Histological sections from 57 urothelial neoplasms were stained immunohistochemically for TII-α expression; the percentage of positive cells in the area of greatest staining was recorded as the TII-α index. RESULTS: TII-α nuclear staining was positive in all the samples except one. The mean (SD) TII-α index was 10.7 (5.9) in urothelial neoplasms of low malignant potential (grade 1), 15.5 (5.0) in low-grade (grade 2) and 42.1 (13.4) in high-grade urothelial carcinoma (grade 3). The mean TII-α index was 10.7 (5.9), 26.3 (14.8) and 44 (19) in stages pTa, pT1 and pT2, respectively. The TII-α index was significant for predicting death from cancer, independently of the stage or grade of the disease (P = 0.019, hazard ratio 1.1). CONCLUSIONS: A higher TII-α index indicates a greater probability of recurrence of disease and lower overall survival. Therefore TII-α expression has prognostic value in bladder carcinoma.