Immunohistochemical evaluation of p53, proliferating cell nuclear antigen (PCNA) and bcl-2 expression during bacillus calmette-guerin (BCG) intravesical instillation therapy for superficial bladder cancers

Bacillus Calmette-Guerin (BCG) immunotherapy for superficial bladder cancer is now widespread, but non-effective cases are not uncommon and it has yet to be clarified why this is the case. In an attempt to cast light on this problem, we evaluated differences between effective and non-effective cases immunohistochemically using p53, proliferating cell nuclear antigen (PCNA), and bcl-2 antibodies. Between March 1988 and March 1996 a total of 79 superficial bladder cancer patients were treated with BCG intravesical instillation therapy after transurethral resection of bladder tumor (TUR-Bt). Of these, 19 demonstrated recurrence after the initial treatment. From the 60 remaining patients without recurrence, we randomly chose 19 additional cases and evaluated both series for p53, PCNA and bcl-2 immunohistochemical staining using formalin-fixed, paraffin-embedded tissues. For the recurrent cases, material taken prior and subsequent to BCG therapy was available for 17 of the 19 patients. Positive staining for p53 was noted for 42.1% (8/19) of both recurrent and non-recurrent cases, without any difference between the two. The rates for PCNA and bcl-2 were 52.6% (10/19) and 47.4% (9/19) in recurrent, and 36.8% (7/19) and 78.9% (15/19) in non-recurrent cases, respectively. Thus, there was a significant difference for lower incidences of bcl-2 in recurrent cases (P=0.044). Values for p53 and bcl-2 were respectively 47.1% (8/17) and 41.2% (7/17) pre-treatment, and 52.9% (9/17) and 35.3% (6/17) post-treatment in the recurrence group. In contrast to the similarity in these results, PCNA positive cases were 52.9% (9/17) pre-treatment and 17.6% (3/17) post-treatment. These data suggest that there are differences between BCG-sensitive and BCG-resistant bladder cancers in terms of bcl-2 expression. Received: 25 August 1997 / Accepted: 5 February 1998