Apoptotic cell death and Smad4 expression in transitional cell carcinoma of the renal pelvis and ureter

Purpose: To investigate the frequency of apoptosis and the expression or Smad4 protein as well as their roles in transitional cell carcinoma (TCC) of the renal pelvis and ureter. Methods: Apoptosis was detected by using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) technique in 34 formalin-fixed and paraffin-embedded specimens of renal pelvic and ureteral TCC. The expression or Smad4 was immunohistochemically studied. Results: The incidence of apoptosis ranged from 1.10 to 3.75% with a median or 2.50% in TCC of the renal pelvis and ureter. The incidence of apoptosis was noted to be closely related to histologic grade but not to pathologic stage of the cancer. The expression of Smad4 was detected in six of 34 cases (17.6%). Regarding subcellular distribution, Smad4 protein was localized both in cytoplasm and nucleus of the cancer cells. In comparing the incidence of apoptosis with the expression of Smad4, no significant associations were seen between them. The expression or Smad4 was not related to the tumor grade nor stage of the cancer. Conclusions: The present study demonstrated close association of the incidence of apoptosis with the tumor grade of TCC of the renal pelvis and ureter. Significance of Smad4 expression was not noted in the study. It suggests that apoptotic cell death may play an important role in the tumor progression of renal pelvic and ureteral TCC.