Survivin Expression in Patients with Non-Muscle-Invasive Urothelial Cell Carcinoma of the Bladder

Objectives: Survivin is a member of the inhibitor of apoptosis gene family that controls mitotic progression and induces tumor cell invasion. Our objectives were to evaluate the association of survivin expression with the presence of urothelial cell carcinoma of the bladder and clinical outcomes in patients with non-muscle-invasive urothelial cell carcinoma of the bladder. Methods: Immunohistochemical staining for survivin was performed on archival bladder tissue microarray specimens from 9 normal controls and 74 consecutive patients who had Stage Ta, Tis, and/or T1 disease on transurethral resection (TUR). Staining was also performed on cystectomy specimens from 22 of these patients who had undergone radical cystectomy for disease progression. Survivin was considered overexpressed when more than 10% of the cells expressed survivin. Results: Survivin was not expressed in normal bladder urothelium. Survivin was overexpressed in 53% of non-muscle-invasive bladder tumors. Overexpression of survivin was associated with greater tumor grade (P <0.001). On multivariate analyses adjusted for the effects of TUR stage, grade, and intravesical therapy, survivin overexpression was independently associated with cancer recurrence (hazard ratio 2.50, 95% confidence interval 1.09 to 5.69, P = 0.02) and progression (hazard ratio 3.87, 95% confidence interval 1.13 to 13.24, P = 0.03), but not disease-specific survival (hazard ratio 1.88, 95% confidence interval 0.90 to 6.46, P = 0.07). A high concordance rate for survivin expression was found between the 22 matched TUR and cystectomy specimens (86%). Conclusions: Survivin expression analysis performed on TUR specimens might help identify patients with non-muscle-invasive urothelial cell carcinoma of the bladder at high risk of disease recurrence and progression who would benefit from closer follow-up or more aggressive therapy.