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Expression patterns of erbB receptor family in normal urothelium and transitional cell carcinoma. An
1Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan, Republic of China. chownh@mail.ncku.edu.tw
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.
Insights
Class I tyrosine kinase receptors, including epidermal growth factor receptor (EGFR) and ErbB family members, show distinct expression patterns in normal bladder cells. Their altered expression in urothelial carcinoma may influence tumor invasion.
Area of Science:
- Urothelial Carcinogenesis
- Receptor Tyrosine Kinases
- Cellular Homeostasis
Background:
- Class I tyrosine kinase receptors, encompassing EGFR, ErbB2, ErbB3, and ErbB4, play roles in cellular processes.
- Understanding their expression is crucial for elucidating mechanisms of normal urothelial function and bladder cancer development.
Purpose of the Study:
- To investigate the differential expression of class I tyrosine kinase receptors in normal urothelium and urothelial carcinoma.
- To correlate receptor expression patterns with cellular proliferation markers and tumor characteristics.
Main Methods:
- Immunohistochemistry was employed to examine the expression of EGFR, ErbB2, ErbB3, and ErbB4 in normal and cancerous urothelial tissues.
- Expression levels were analyzed in relation to BCL-2 protein, Ki-67 antigen (MIB-1), tumor grade, and muscular invasion.
Main Results:
- EGFR exhibited basal cell localization, while ErbB2, ErbB3, and ErbB4 were predominantly found in the superficial layer of normal urothelium, demonstrating reciprocal distribution.
- EGFR expression positively correlated with BCL-2 and Ki-67, whereas ErbB2, ErbB3, and ErbB4 showed inverse correlations.
- In urothelial carcinoma, EGFR overexpression was linked to muscular invasion, and coexpression of EGFR-ErbB3 and ErbB3-ErbB4 correlated with advanced tumor invasion.
Conclusions:
- Class I tyrosine kinase receptors display distinct, reciprocal expression patterns in normal urothelium.
- The coordinated expression observed in normal tissue is disrupted during tumorigenesis, suggesting altered roles in bladder cancer progression and invasion.