Materials and Methods: Apoptosis was detected by in situ end-labeling of fragmented DNA using the terminal deoxynucleotidyl transferase reaction in 45 paraffin-embedded primary transitional cell carcinoma specimens, 9 metastatic lymph nodes and 5 normal bladder specimens. The proliferation status of the tumor cells among the same bladder cancer specimens was evaluated by using a monoclonal antibody that recognizes the proliferation-associated nuclear antigen, Ki-67.

Results: The apoptotic index of normal transitional epithelium (0.06%) was significantly lower than that of all grades of transitional bladder carcinoma (p = 0.006). Although the apoptotic index of transitional carcinomas increased with increasing grade, this difference failed to achieve statistical significance, ranging from 0.54+/-.23% in grade I to 1.24+/-.77% in grade III. The proliferative index, as determined by Ki-67 positivity, also increased with increasing grades of tumor (12.8+/-8.4% in grade I to 22.6+/-15.2% in grade III) and was significantly greater than in normal urothelium (0.64+/-0.52%, p = 0.003). Bcl-2 expression was significantly lower in the normal transitional epithelium and in the well and moderately differentiated tumors (grades I-II) when compared with poorly differentiated (grade III) tumors (p =.004), The incidence of bcl-2 expression in all bladder specimens analyzed was uniformly low (<5.3%). Transforming growth factor-beta(1) expression was not detected in any of the normal bladder specimens, primary tumors, or metastatic lymph nodes analyzed.

Conclusions: The present findings revealed that no statistically significant correlation exists between the frequency of apoptosis and the pathological stage of bladder tumors, while they clearly demonstrate a strong direct correlation between an increased rate of cell proliferation and bladder cancer progression.