Low Expression of EphB2, EphB3, and EphB4 in Bladder Cancer: Novel Potential Indicators of Muscular Invasion
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Purpose: Eph receptors are differentially expressed in numerous malignant tumors. This study intended to analyze the roles ofEphB receptors (EphB2, B3, and B4) in urinary bladder cancer. Materials and Methods: Tissue microarray-based immunohistochemical analysis was used to investigate the expression patternsof EphB2, EphB3, and EphB4 in 154 bladder cancer specimens. Immunohistochemical staining was conducted examining theextent of stained cells and staining intensity. EphB was considered to be highly expressed when the intensity of staining was morethan moderate in >25% of cells in the tissue section. Small interfering RNA (siRNA) was used to knock down EphB expression inbladder cancer cell lines (T24, 5637) to determine the effects of EphB on tumor cell invasion, proliferation, and migration. Results: EphB receptors (B2, B3, and B4) were detected in 40.9% (EphB2, 63/154), 71.4% (EphB3, 110/154), and 53.2% (EphB4,82/154) of bladder cancer specimens. Low expression of EphB2, B3, and B4 receptors were significantly associated with higher tumorgrade (EphB2, p<0.001; EphB3, p=0.032; EphB4, p<0.001) and muscular invasion (EphB2, p=0.002; EphB3, p=0.009; EphB4,p<0.001). No obvious correlation was observed with other clinicopathological variables, such as age, sex, recurrence, lymph nodeinvolvement, metastasis, and overall survival. Inactivation of EphB receptors by siRNA transfection increased cell viability, tumorcell invasion, proliferation, and migration in comparison with untransfected cancer cells. Conclusion: Low expression of EphB receptors (B2, B3, and B4) can be a predictive marker for muscular invasion of bladder cancer.
Abstract
Purpose: Eph receptors are differentially expressed in numerous malignant tumors. This study intended to analyze the roles ofEphB receptors (EphB2, B3, and B4) in urinary bladder cancer. Materials and Methods: Tissue microarray-based immunohistochemical analysis was used to investigate the expression patternsof EphB2, EphB3, and EphB4 in 154 bladder cancer specimens. Immunohistochemical staining was conducted examining theextent of stained cells and staining intensity. EphB was considered to be highly expressed when the intensity of staining was morethan moderate in >25% of cells in the tissue section. Small interfering RNA (siRNA) was used to knock down EphB expression inbladder cancer cell lines (T24, 5637) to determine the effects of EphB on tumor cell invasion, proliferation, and migration. Results: EphB receptors (B2, B3, and B4) were detected in 40.9% (EphB2, 63/154), 71.4% (EphB3, 110/154), and 53.2% (EphB4,82/154) of bladder cancer specimens. Low expression of EphB2, B3, and B4 receptors were significantly associated with higher tumorgrade (EphB2, p<0.001; EphB3, p=0.032; EphB4, p<0.001) and muscular invasion (EphB2, p=0.002; EphB3, p=0.009; EphB4,p<0.001). No obvious correlation was observed with other clinicopathological variables, such as age, sex, recurrence, lymph nodeinvolvement, metastasis, and overall survival. Inactivation of EphB receptors by siRNA transfection increased cell viability, tumorcell invasion, proliferation, and migration in comparison with untransfected cancer cells. Conclusion: Low expression of EphB receptors (B2, B3, and B4) can be a predictive marker for muscular invasion of bladder cancer.
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