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

Abstract

To investigate the immunohistochemical expression of topoisomerase II-alpha (TII-alpha, 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. Histological sections from 57 urothelial neoplasms were stained immunohistochemically for TII-alpha expression; the percentage of positive cells in the area of greatest staining was recorded as the TII-alpha index. TII-alpha nuclear staining was positive in all the samples except one. The mean (sd) TII-alpha 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-alpha index was 10.7 (5.9), 26.3 (14.8) and 44 (19) in stages pTa, pT1 and pT2, respectively. The TII-alpha index was significant for predicting death from cancer, independently of the stage or grade of the disease (P = 0.019, hazard ratio 1.1). A higher TII-alpha index indicates a greater probability of recurrence of disease and lower overall survival. Therefore TII-alpha expression has prognostic value in bladder carcinoma.