Intravesical bacillus calmette-guerin (BCG) as inducer of tumor-suppressing proteins p53 and p21 Waf1-Cip1 during treatment of superficial bladder cancer.
OBJECTIVE
Previous in vitro investigations recorded an inhibition of cell proliferation by BCG when added to different cell cultures. The induction of apoptosis by BCG is controversial. Our study aimed to evaluate the influence of BCG on the expression of tumor suppressing proteins p53 and p21Waf1-Cip1 and apoptosis of the urothelial cells in vivo.


METHODS
Twenty-one cases of superficial bladder cancer, treated with TUR and subsequent intravesical BCG, were studied retrospectively. The assays evaluated the expression of p53 and p21Waf1-Cip1 by immunochemistry (IHC), and the presence of apoptosis by TUNEL assay. The estimates were performed, in each case, on the following specimens: one tumor sample and one non-neoplastic sample collected during the TUR which preceded the administration of BCG; one non-neoplastic sample collected 3 months after the diagnosis; and one non-neoplastic sample collected in the first 2 weeks after the completion of the treatment. Samples of 6 cancer recurrences detected during BCG were examined too.


RESULTS
As usual for non-neoplastic urothelium, the pre-BCG samples displayed poor p53 and p21Waf1-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.


CONCLUSIONS
The relationship between changes of the IHC features and BCG suggests that BCG, at least under some circumstances, can induce the activation of wild type p53 and p21Waf1-Cip1 in the urothelium. The mechanism of the BCG-p53 status interaction and its role in the antitumor activity of BCG remain to be clarified.
Fontana
D
D
Department of Clinical and Biological Sciences, University of Turin, S. Luigi Hospital, Orbassano, Italy.
Bellina
M
M
Galietti
F
F
Scoffone
C
C
Cagnazzi
E
E
Guercio
S
S
Cappia
S
S
Pozzi
E
E
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001500:BCG Vaccine / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D016159:Tumor Suppressor Protein p53