ErbB2, ErbB3 and ErbB4 expression in urothelial tumors of the upper urinary tract and their prognostic significance.

PURPOSE: ErbB family represents a promising therapeutic target in upper urinary tract urothelial carcinoma (UUTUC). Our study aimed to correlate ErbB2, ErbB3 and ErbB4 expression in UUTUC with other clinicopathological parameters as well as patient outcome. METHODS: ErbB2, ErbB3 and ErbB4 were immunohistochemically assessed in 99 consecutive UUTUC specimens. RESULTS: With a median follow-up of 52.5 months (range 1-127) 28 patients (28.3%) died 1-95 months after the first surgical treatment and the mean survival was 18.9-24.2 months. ErbB2, ErbB3 and ErbB4 expression was positive in 64.8, 19.5, and 20.8% of the tumors, respectively. Combined expression of all 3 receptors was found in 7.9% of the tumors, combined expression of 2 receptors in 14.5% and 48.7% expressed at least one ErbB receptor. No ErbB expression was found in 28.9% of the tumors. We found no significant correlation between ErbB2, ErbB3 and ErbB4 expression with tumor stage, grade, recurrence or cancer specific survival apart from the inverse relation between ErbB2 expression and time to recurrence (p=0.027). CONCLUSION: Of the 3 receptors evaluated, neither ErbB3 nor ErbB4 showed any prognostic significance in the UUTUC. ErbB2, however, was inversely associated with recurrence and needs further evaluation in well-designed, prospective, randomized trials.