EXPRESSION PATTERNS OF ERBB RECEPTOR FAMILY IN NORMAL UROTHELIUM AND TRANSITIONAL-CELL CARCINOMA - AN IMMUNOHISTOCHEMICAL STUDY

The class I tyrosine kinase growth-factor receptors include epidermal growth factor receptor (EGFR), ErbB2 (c-erbB-2, HER-2/neu), ErbB3 and ErbB4. To elucidate their role in the regulation of homeostasis and ca rcinogenesis, we examined the expression of the receptors in normal ur othelium and in urothelial carcinoma by immunohistochemistry. EGFR was expressed in the basal cells of normal urothelium, while ErbB2, ErbB3 and ErbB4 were present mainly in the superficial layer. A distinct re ciprocal distribution was observed between the EGFR and the remaining members of the subclass (P = 0.0001). Both BCL-2 protein and Ki-67 ant igen (MIB-1) showed a strong positive association with EGFR (P = 0.002 ) and an inverse correlation with ErbB2, ErbB3 or ErbB4 (P = 0.0004, 0 .0000, and 0.001, respectively). With regard to carcinoma, there was n o important relationship between receptor overexpression and tumour gr ading (P > 0.1), while only EGFR overexpression was correlated with mu scular invasion (P = 0.02). Coexpression of EGFR-ErbB3 and ErbB3-ErbB4 was more often detected in high-grade tumours and correlated with the extent of tumour invasion. Our data indicate that class I receptors a re differentially expressed in normal urothelium in vivo, but an orche strated expression pattern does not exist during tumorigenesis.