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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Koren
R
R
Department of Pathology, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel. rumelia@isdnmail.co.il
Kugel
V
V
Dekel
Y
Y
Weissman
Y
Y
Livne
P M
PM
Gal
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm; D002295:Carcinoma, Transitional Cell / Q000201:enzymology*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000201:enzymology*
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human