The Expression And Their Significance Of C-IAP1/2 In Human Bladder Cancer

Bladder cancer is one of the most common maliganency of the urinary system. Up to now, the main treatment for bladder cancer is a variety of surgical operation plus postoperative intravesical instillation. However, about more than half of the tumors will recurrence within 2 years after surgery, and 10%～15% of the recurrences progress to higher stage/grade and become more resistant to chemotherapy. Inhibition of apoptosis allows prolonged survival of tumor cells, and contribute to tumor cell to escape immune surveillance, such as radiotherapy and chemotherapy induced cell death, is an important mechanism of tumor development. Therefore, the current study, more and more focus on apoptosis and proliferation of cancer cells, thus improving treatment.IAPs (inhibitor of apoptosis protein) is a very important anti-apoptotic factor, a common feature of the family structure is the N-terminal 1 or 3 containing 70 amino acids containing baculovirus IAP repeat (BIR), carboxyl Side with or without a ring finger. It can inhibit the activity of caspases and mitochondrial precursor protein for example against Smac/DIABLO release, the internal and external blocking apoptotic pathways. Up to now,8 mammalian IAP members have been identified, including cIAPl, cIAP2, XIAP, Survivin, Livin, NAIP, BRUCE, and ILP2. Recent research has proved:IAPs not only play important roles in regulating cell apoptosis, but also widely participate in the process of mitosis, ubiquitin-proteasome pathway, MAPK mitogen-activated protein kinase and NF-κB signaling pathways. Overexpression of IAPs and cancer evolution and phase-associated resistance to chemotherapy and is associated with poor prognosis.In the IAPs, because Livin and Survivin in tumor-specific characteristics (they have specific expression of cancer, but very low in normal tissue) more attention by researchers. However, in patients with bladder cancer, Livin and Survivin expression is only a small number, therefore, limit their prediction and therapeutic value.cIAPs (cIAP1 and cIAP2), in many normal tissue types have a wide range of expression. Previous studies showed that the tumor is often overexpressed in cIAPs, and accompanied by apoptosis and value. However the differential expression of cIAPs between normal bladder urothelium and bladder transitional cell carcinoma is still unclear. The study identified bladder cancer and normal bladder epithelium with cIAPl and cIAP2 expression and distribution, while we compared the gene expression data with the corresponding clinical and significance of pathological tumor characteristics.Material and method:Immunohistochemistry was performed to analyze the expression of cIAPl and cIAP2 in the bladder cancer and normal bladder urothelium specimens. Samples archive material from dalian medical university pathologists in January 2004 between December 2005 for these analyses. Our study archive material of 92 cases. Collection of pathologically confirmed 86 cases of bladder cancer samples. The male 66 patients and female 20 patients;multiple Bladder cancer 64 patients and single Bladder cancer 22 patients; According to the 2002 TNM pathological staging system (UICC) divided into muscularis non-invasive bladder cancer (Tis, Ta, Tl) 58 patients and muscularis invasive bladder cancer (T2 or more) 28 patients;According to the histologic differentiation degree (1973 WHO pathologic stage) is divided into:gradeⅠwell-differentiated cancers 60 patients, gradeⅡdifferentiation carcinoma 16 patients, gradeⅢpoorly differentiated carcinoma 10 patients. As controls, normal-appearing bladder tissues were obtained in an area at a distance more than 1cm away from the organization of the tumor region in 20 patients. No evidence of histological changes in the normal control bladder samples was histopathologically observed. For cIAPl-C and cIAP2-C assessment, staining intensity was scored as 0 (negative),+1 (weak),+2 (medium), and +3 (strong). For cIAPl-N, staining intensity was calculated as 0 (0%), +1 (1-25%),+2 (26-50%), and +3 (> 50%) record by averaging 5 randomized microscopic fields According to the tumor cells are stained cells were calculated as a percentage of the total.Results:Compared with normal bladder epithelium, patients with bladder cancer cIAP1 and cIAP2 expression was significantly increased, (cIAP1-C:P<0.01, cIAP2-C:P<0.01, cIAP1-N:P<0.01). In nuclear c-IAP1 expression, patient gender and tumor number no significant difference, the pathological staging of bladder cancer (muscle myometrial invasion and non-infringement, P<0.01) and pathological Grade (poorly differentiated and well differentiated, P<0.01) were significantly different.Conclusion:(1) c-IAP1 and c-IAP2 have a dissimilarity distribution. c-IAP 1 not only in the cytoplasm, can also be seen in the nucleus, c-IAP2 only in the cytoplasm.(2) c-IAP1/2 in bladder cancer tissues was significantly higher than that of normal bladder epithelium, the differences were statistically significant.(3) Nuclear cIAP-1 expression was significantly over-expression in bladder cancer and associated with tumor stage/grade and tumor invasion. Thus, Tip cIAP1-N may be a useful predictor of the prognosis of bladder cancer and bladder cancer gene therapy effective index.