Expressions of Epidermal Growth Factor Receptor, c-erbB-2 and p53 Protein as Useful Markers of Malignant Potential in a Transitional Cell Carcinoma of the Urinary Bladder

ABSTRACT

Transitional cell carcinoma(TCC) of the urinary bladder shows marked heterogeneity in biological behaviors. Evidence has accumulated that biological markers may provide significant information to predict the potential aggressiveness of TCC. We have assessed the expression of the epidermal growth factor receptor (EGF-R), c-erbB-2 and p53 proteins in 56 cases of TCC to investigate the prognostic significance of differential expression of these oncoproteins using an immunohistochemical method. We analysed the expression patterns of these oncoproteins according to tumor stage and grade. And we assessed the probability of progression-free survival in stage T1 tumors according to their expressions. Positive rates of EGF-R (>+3 staining intensity), c-erbB-2 (intense membrane staining) and p53 proteins (>20% positive cells) were 73.2%, 37.5% and 42.9%, respectively. Invasive tumors had significantly higher positive rates of all three factors than did superficial tumors (p<0.005 for EGF-R and c-erbB-2, p<0.05 for p53). High grade tumors had significantly higher positive rates of c-erbB-2 and p53 proteins (p<0.005). In superficial tumors, T1 tumors had higher positive rate of p53 protein compared with Ta tumors (p<0.05). Twelve cases of superficial tumors (34.3%) were positive for EGF-R and negative for c-erbB-2 and p53 proteins. Nine cases of superficial tumors(25.7%) were negative for all three factors. In invasive tumors, however, 42.5% of the cases were positive for all three factors. The overexpression of p53 protein was the only useful marker to predict the rapid progression in stage T1 tumors (p<0.05, log-rank test). These results suggest that the differential overexpression of EGF-R, c-erbB-2 and p53 proteins could be useful to depict tumor aggressiveness of TCC of the urinary bladder. And, the overexpression of a p53 protein may be a useful marker to predict the possibility of rapid progression in stage T1 tumors.