Intravesical Bacillus Calmette-Guerin (BCG) as inducer of tumor-suppressing proteins p53 and p21(Waf1-Cip1) during treatment of superficial bladder cancer

Purpose: Previous in vitro investigations recorded an inhibition of cell pr oliferation by BCG when added to different cell cultures. The induction of apoptosis by BCG is controversial. Our study aimed to evaluate the influenc e of BCG on the expression of tumor suppressing proteins p53 and p21(Waf1-C ip1) and apoptosis of the urothelial cells in vivo. Materials and Methods: Twenty-one cases of superficial bladder cancer, trea ted with TUR and subsequent intravesical BCG, were studied retrospectively. The assays evaluated the expression of p53 and p21(Waf1-Cip1) by immunoche mistry (IHC), and the presence of apoptosis by TUNEL assay. The estimates w ere performed, in each case, on the following specimens: one tumor sample a nd one non-neoplastic sample collected during the TUR which preceded the ad ministration of BCG; one non-neoplastic sample collected 3 months after the diagnosis; and one non-neoplastic sample collected in the first 2 weeks af ter the completion of the treatment. Samples of 6 cancer recurrences detect ed during BCG were examined too. Results: As usual for non-neoplastic urothelium, the pre-BCG samples displa yed poor p53 and p21(Waf1-Cip1) immunoreactivity. By contrast, the samples collected during and in the aftermath of BCG showed an overall increase of the expression of both proteins. The rare occurrence of apoptosis proved to be chronologically unrelated to the BCG treatment. Discussion: The relationship between changes of the IHC features and BCG su ggests that BCG at least under some circumstances, can induce the activatio n of wild type p53 and p21(Waf1-Cip1) in the urothelium. The mechanism of t he BCG-p53 status interaction and its role in the antitumor activity of BCG remain to be clarified.