Expression of c-erbB-2 protein in normal and neoplastic urothelium: lack of adverse prognostic effect in human urinary bladder cancer

Abstract

The clinical significance of c-erb B-2 expression in urinary bladder cancer remains controversial. We performed an immunohistochemical study to examine the expression of c-erb B-2 in non-neoplastic urothelium (n = 12) and transitional cell carcinoma of the urinary bladder (n = 82). c-erb B-2 protein was localized in superficial and some intermediate cells of non-neoplastic urothelium. A total of 29 out of 82 (35%) tumors were positive for c-erb B-2 over-expression. There was no significant association of c-erbB-2 expression with tumor grade (p = 0.12), stage (p = 0.93), DNA ploidy status (p = 0.56) and the sex of patients (p = 0.5). Expression of epidermal growth factor receptor and Ki-67 index was available in 33 cases. Both parameters showed no apparent association with c-erbB-2 expression (p = 0.53 and 0.58 respectively). Factors correlated with poor patient survival by univariate analysis were tumor stage (p = 0.0001), tumor grade (p = 0.001), development of second recurrence (p = 0.002) and negative expression of c-erbB-2 (p = 0.017). Important indicators associated with first recurrence were tumor stage (p = 0.028), and c-erbB-2 expression with the risk of second recurrence (p = 0.031). Multivariate survival analysis revealed that tumor stage was among the most important prognostic factors (p = 0.029), followed by tumors without c-erbB-2 expression (p = 0.031) with a median follow-up at 46 months. The age of patients and c-erbB-2 expression were significantly associated with developing second recurrence (p = 0.031 and 0.046 respectively). The results indicate that expression of c-erbB-2 is independent of the stage and grade of bladder cancer. Although c-erbB-2 status can discriminate subpopulations with a high risk of recurrence, evaluation of its expression in paraffin-embedded tumors does not indicate poor prognosis for patients with urinary bladder cancer. To address this discrepancy a better understanding of the regulatory mechanism and physiological properties of c-erbB-2 protein in urothelium is required.