Study On The Expression Of Survivin In Bladder Transitional Cell Carcinoma

Obstractive Survivin is a new member of the inhibitors of apoptosis proteins (IAP) family, selectively overexpressed in common human cancers but not in normal adult tissues, and associated with aggressiveness of the disease and unfavorable outcomes. To study the expression of Survivin gene in bladder transitional cell carcinoma (BTCC) tissue and exfoliated urine/ urothelial cell (EUC), and the correlation between expression of Survivin and the biological behaviors of BTCC ,in order to disclose the moleculor mechanism and explore diagnostic practable of Survivin in urine specimens.Methods Immunohistochemistry ( PV-9000)was used to detect the expression of Survivin and apoptosis associated factors (Fas, FasL, PCNA, P-GP) in BTCC (n=64), bladder benign lesions (n=15) and normal bladder mucosa (n=12);Survivin mRNA was investigated using RT-PCR analysis in tumor tissues and Survivin protein was investigated using Western blot analysis in the urine specimens ,in order to explore the expression of Survivin gene and the clinicopathological parameters. Results Immunohistochemistry indicated that the expression level of Survivin in BTCC(93.8%) was higher than bladder benign lesions(66.7%) and normal bladder mucosa (0) (P<0.01). The expression level of Survivin was strongly correlatated with pathological grade. The Fas expression level among BTCC, bladder benign lesions and normal bladder mucosa was 50%, 80% and 100% , respectively (P<0.01).TheFasL expression level among BTCC, bladder benign lesions and normal bladder mucosa was 90.6% > 60% and 16.7% respectively (P<0.01). The expression of P-GP in BTCC(53.1%) was higher than benign lesions (40%) and normal bladder mucosa (0. 08%,l/12) , The expression level of P-GP was strongly correlated with pathological grade and tumor recurrence (P<0.01). PCNA index (PI)was different in BTCC(64.44± 44.54%), bladder benign lesions(36.33± 23.52%) and normal bladder mucosa (17.67+11.43%) (P<0.01);The expression of PI was strongly correlated with pathological grade,clinical stage and tumor recurrence (P<0.01).RT-PCR indicated that the expression level of Survivin in BTCC(n=40)was 100% and in normal bladder mucosa(n=12) was 0%.Western blot indicated that the expression level of Survivin in BTCC (n=40) was 95% and in the control (n=32) was 6.25%(P<0.01).There was no stastics significance between AO-F (acridine orange fluorescope) and Survivin protein in urine exfoliated cells (P>0.05) . Conclusion It indicated that Survivin was the diagnostic and prognostic index of BTCC ,and it provided theory basis about the gene target therapy in BTCC.Survivin may have a synergic role with the apoptosis associated factors (PCNA> Fas/FasL) and play a important role in the iniation and progression of BTCC. The MDR (P-GP) of BTCC was strongly correlated with the expression of P-GP and Fas, but was not correlated with the Survivin expression .It may provide evidence to increase the chemotherapy sensitivity by MDR reversing agent and Fas interference.There is a close relationship between the expression of Survivin mRNA in tissues and protain in exfoliated urine cells and the biological behavior of TCC.The findings suggest that Survivin in exfoliated urine cells can truly reflect the expression of Survivin intumors and be used as a noninvasive method for the diagnosis and prognostic supervision of BTCC.The specific and sensitive were high of Survivin in exfoliated urine cells, Survivin in adjunct to AO-F may have a high sensitivity in diagnostic BTCC.