Objectives: To investigate expression patterns of erbB receptors in a panel of 58 human bladder tumors. Aberrant functional and structural interactions of erbB type I receptor tyrosine kinase cell surface receptors are important in the development and maintenance of the malignant phenotype. Few studies have focused on the remaining family members or patterns of receptor coexpression in urothelial cancer.
Methods: Frozen tumor samples from 58 patients with newly diagnosed bladder cancer were collected; 18 had Stage Ta, 20 Stage T1, and 20 had Stage T2 or worse. The grade was G1 in 5, G2 in 24, and G3 in 29 patients. Seven normal urothelial samples were obtained from patients with benign urologic conditions. The tumor material was probed using conventional immunoblotting and enhanced chemiluminescence. The blots were captured with digital imaging, and protein expression was quantified with gel analysis software.
Results: Most tumors exhibited detectable expression of at least one erbB receptor. Examples of coexpression of epidermal growth factor receptor (EGFr) and erbB-2 were also found. Detectable erbB-3 or erbB-4 protein expression was lacking in this series. Compared with other tumors, the T1 samples exhibited the greatest mean levels of erbB-2 protein expression (P = 0.0028). Of the 58 tumors, 10 (17.2%) coexpressed EGFr and erbB-2; this was associated with T1 disease (P = 0.03).
Conclusions: Varied levels of expression of both EGFr and erbB-2 appear to exist in human bladder cancer. These preliminary data do not support erbB-3/4 as major protagonists in this tumor system. The observations presented suggest a role for EGFr and erbB-2 in the development and progression of bladder cancer that should be explored further.