Expression patterns of erbB receptor family in normal urothelium and transitional cell carcinoma

Abstract

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 carcinogenesis, we examined the expression of the receptors in normal urothelium 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 reciprocal distribution was observed between the EGFR and the remaining members of the subclass (P = 0.0001). Both BCL-2 protein and Ki-67 antigen (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 no important relationship between receptor overexpression and tumour grading (P > 0.1), while only EGFR overexpression was correlated with muscular 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 are differentially expressed in normal urothelium in vivo, but an orchestrated expression pattern does not exist during tumorigenesis.

Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma

“…This phenomenon was found in previous in vitro studies as well as a clinical study using surgical specimens for transitional cell carcinoma (Kim et al, 1994;Soltoff et al, 1994;Chow et al, 1997). Further studies are needed to find whether the relationship is due to heterodimerization of these receptors in this carcinoma.…”

“…Thus far, of the four receptors, the expression of EGF-R and c-erbB-2 has been investigated in various neoplasms, including malignancies of the liver and biliary tract (Brunt and Swanson, 1992;Collier et al, 1992;Nakapoulou et al, 1994;Lee and Pirdas, 1995;Kira et al, 1997;Terada et al, 1998). The other two receptors, c-erbB-3 and c-erbB-4, have only been studied in depth for a few neoplasms (Sanidas et al, 1993;Simpson et al, 1995;Shintani et al, 1995;Haugen et al, 1996;Travis et al, 1996;Bobrow et al, 1997;Bodey et al, 1997;Chow et al, 1997;Ibrahim et al, 1997;Srinivasan et al, 1998Srinivasan et al, , 2000Suo et al, 1998;Freiss et al, 1999;Haussler et al, 1999;Kapitanovic et al, 2000;Kew et al, 2000), and little is known about their expression in hepatic malignancies. In this study, we investigated the expression of all four components of this family in a large series of HCC to evaluate their clinical significance and to identify the factors reflecting the development of this carcinoma.…”

bcl-2 Expression in Cholangiocellular Carcinoma Is Inversely Correlated with Biologically Aggressive Phenotypes

“…Subsequent studies have revealed that the bcl-2 protein plays a crucial role in prolonged cell survival by inhibiting apoptosis [4, 5, 6]. Previous in vivo studies have demonstrated that bcl-2 is detectable in the basal cells of the intestinal epithelium and urothelium [7, 8], but not in the superficial and more differentiated cells, suggesting that bcl-2 plays a role in negatively regulating cell differentiation from stem cells in order to prolong cell survival. bcl-2 expression was also observed in the epithelium of the breast and prostate, which are hormonally regulated, although its role in these epithelia is less clear [7].…”

Growth factors and receptors as prognostic markers in urothelial carcinoma

“…The localization of expression in the urothelium appears to differ between normal and carcinomatous urothelium, with staining confined to the basal layers of normal urothelium and all layers of transitional cell carcinoma [9]. The subcellular localization may also be important.…”