Distinctive Expression Pattern of ErbB Family Receptors Signifies an Aggressive Variant of Bladder Cancer

Abstract

Expression of various members of the ErbB family (EGFR/ErbB-1, ErbB-2, ErbB-3, and ErbB-4) has been associated with stage of disease and survival in patients with urothelial carcinoma (UC). We examined the correlation of expression of ErbB family receptors with progression of UC, and survival. A UC tissue array was constructed from 248 archival paraffin blocks, and quality control studies were ascertained. The tissue microarray was stained for EGFR, ErbB-2, ErbB-3, and ErbB-4, and was analyzed using an automated reader. Patient data included grade, stage, growth pattern, recurrence, and survival. Kaplan-Meier estimates of the 5-year overall and recurrence-free survival were 58% and 27%, respectively. Patients with high-grade, invasive, or non-papillary disease had a worse prognosis than patients with low-grade, superficial, or papillary disease (p <0.0001). High EGFR or low ErbB-4 expression was associated with non-papillary, high-grade, and invasive tumors (p <0.002), as well as a significantly shorter recurrence-free survival (p = 0.028) and overall survival (p = 0.047), respectively. Levels of ErbB-2 and ErbB-3 expression were not associated with overall or recurrence-free survival. The expression profiles of ErbB-4 and EGFR are prognostic in UC and may help in selecting high-risk patients with bladder cancer for more aggressive therapy.