Expression profiles of ErbB family receptors and prognosis in primary transitional cell carcinoma of the urinary bladder

In vitro experiments have demonstrated that epidermal growth factor (EGF)-r elated peptides activate distinct subsets of ErbB receptors and differ in t heir biological activities, The implications of cross-talk among ErbB famil y receptors in human cancer, however, remain to be clarified. This cohort s tudy was performed to examine the expression patterns of ErbB receptors by immunohistochemistry in primary human bladder cancer (n = 245) and compared with conventional biological indicators for their prognostic significance. Expression of individual EGF receptor (EGFR) and ErbB2, ErbB3, or ErbB4 re ceptors was detected in 72.2, 44.5, 56.3, and 29.8 % of bladder cancer case s, respectively, Expression of two of the receptors varied from 14.7 to 42. 4%, of three of the receptors between 11.0 and 22.0%, and of all four of th e ErbR receptors by 8.6%. Important indicators in association with patient survival were tumor staging (P = 0.017), ErbB2 (P = 0.018), EGFR-ErbB2 (P = 0.023), and ErbB2-ErbB3 (P = 0.042). In the subset of grade-2 tumors, EGFR -ErbB2-ErbB3 and EGFR-ErbB2 predicted the development of second recurrence (P = 0.026 and 0.039, respectively), and ErbB2-ErbB3 tended to correlate wi th patient survival (P = 0.09). The results indicate that a combination of EGFR, ErbB2, and ErbR3 expression profile may be a better prognostic indica tor than any family member alone. Given that ErbB2 is the preferred coexpre ssion partner of ErbB family members, expression of other ErbB receptors ma y significantly affect the prognostic implication of ErbB2 for bladder canc er patients.