Expression of transcription factors snail, slug, and twist in human bladder carcinoma

BACKGROUND Slug, snail, and twist are transcription factors that regulate the expression of tumor suppressors such as E-cadherin. In this study, we aimed to examine the expression of these transcription factors in human bladder carcinoma. METHODS We first investigated expression of slug, snail, twist and E-cadherin in five bladder Carcinoma cell lines by reverse transcription-polymerase chain reaction and western blotting. Furthermore, we investigated slug, snail, and twist and E-cadherin expression by immunohistochemistry with bladder carcinoma (tumor, n = 120; background, n = 42). RESULTS Expression of slug mRNA and protein was detected in all cell lines, twist was clearly expressed in two out of five bladder carcinoma cell lines, snail was not expressed, and E-cadherin was detected in 3 cell lines. 44.2% (53/120) of human bladder carcinoma tissues and 38% (16/42) background tissue showed an expression of twist; 62.5% (75/120) of human bladder carcinoma tissues and 40% (17/42) background tissue showed an expression of slug, 15.8% (19/120) of human bladder carcinoma tissues and 76% (32/42) background tissue showed an expression of snail, and 25.8% (31/120) cases were negative for E-cadherin expression in carcinoma tissues. Expression of slug and twist shows increased levels in tumors, whereas snail seems reduced. Statistically significant correlations were found between twist, slug, and E-cadherin expression. Immunohistochemistry analysis showed that twist was elevated with increasing tumor stage (P = 0.001), the grade (P < 0.001), the progression (P = 0.035). Slug was elevated and snail was reduced with increasing nodal involvement (tumor-node-metastasis status) (P = 0.004, P = 0.01). E-cadherin was reduced in expression corresponding with tumor grade (P < 0.01). Positive twist, slug and E-cadherin expression clearly predicted poorer PFS (P = 0.042, P = 0.014, P = 0.001). In the multivariate analysis, only snail and E-cadherin expression were independent prognostic factors for OS (P = 0.002, P < 0.001). CONCLUSIONS These data demonstrate that twist, snail and slug have inappropriate expression in bladder carcinoma and that this may play a part in the progression of human bladder carcinoma.