Variable Bcl-2 phenotype in benign and malignant
lesions of urothelium
Vladimir N. Bilim*, Yoshihiko Tomita, Takashi Kawasaki, Masayuki Takeda, Kota Takahashi
Department of Urology, Niigata University School of Medicine, Asahimachi 1, Niigata 951, Japan
Received 11 August 1997; accepted 11 February 1998
Abstract
We examined Bcl-2, Bax and p53 expression in transitional epithelium, benign lesions derived from transitional epithelium
(Brunn’s nests and inverted papillomas) and transitional cell cancer (TCC) of the upper urinary tract and urinary bladder using
immunostaining of cryostat sections. We also performed Western blot analysis of normal urothelium and TCCs for Bcl-2 and
p53. Immunohistochemical staining showed that Bcl-2 was expressed only on basal layer cells, whereas Bax expression was
restricted to superficial layers in normal transitional epithelium. Benign lesions of the urinary bladder (Brunn’s nests and
inverted papillomas) showed strong immunoreactivity to Bcl-2. Taken together, 16 (17%) TCCs were positive for Bcl-2, 62
(64.6%) TCCs were positive for Bax and 28 (29%) TCCs were positive for p53. The expression of Bcl-2 on TCC had a
statistical correlation with tumor stage, histopathologic grade and p53 protein accumulation. The results suggest that although
Bcl-2 overexpression is detected in normal urothelium and benign lesions of the urinary bladder, it might also contribute to the
high grade tumor malignancy of TCC. 1998 Elsevier Science Ireland Ltd.
Keywords: Bcl-2; Bax; p53; Transitional cell cancer; Apoptosis
1. Introduction
Activation of oncogenes and inactivation of tumor
suppressor genes have been found to play an impor-
tant role in carcinogenesis. p53 is a tumor suppressor
gene which codes a protein arresting progression of
the cell cycle through upregulation of the p21 gene in
response to genotoxic stress, causing DNA damage
[27]. Also, p53 protein itself may induce apoptosis.
p53 gene mutations occur frequently in malignant
tumors, suggesting that this event plays a critical
role in the development and progression of many
types of cancer [10]. Mutated p53 protein has a sig-
nificantly prolonged half-life, which allows it to be
determined by an immunohistochemical method,
and a significant correlation between pathologic
grade and accumulation of mutant p53 has been
reported in many different types of cancer, including
our previous studies in urothelial transitional cell can-
cer [26] and its cell lines [12].
The Bcl-2 protooncogene plays a prominent role in
cell longevity through preventing apoptosis. The Bcl-
2 gene is located on the long arm of chromosome 18
(18q21). It encodes a 26 kDa protein, which contri-
butes to the prolonging of cell survival. It has been
shown that Bcl-2 is important in developing and main-
taining the normal function of lymphoid and epithelial
Cancer Letters 128 (1998) 87–92
0304-3835/98/$19.00 1998 Elsevier Science Ireland Ltd. All rights reserved
PII S0304-3835(98)00055-X
* Corresponding author. Tel.: +81 25 2236161, ext. 2595; fax:
+81 25 2292258.