Expression Of Survivin, Caspase-3 And COX-2 In Gall-bladder Carcinoma And Its Implication

Background and Objective: Gallbladder carcinoma(GBC) is the most popular malignant tumor in bile duct system. In recent years, the incidence rate of GBC is increasing obviously. The development of GBC was a complicated course with multi-gene change. There was a close relationship between carcinogenesis and apoptosis, and caspase-3 plays an important role in apoptosis. Survivin is a protein that inhibits apoptosis, facilitates cell growth and regulates cell division. Caspase-3 is the most important effective proteinase in apoptosis. Survivin induces carcinogenesis by inhibit caspase-3.COX-2 is an inducible enzymes, which is strongly expressed when they suffer from different stimulus, such as growth factors, inflammatory factors, lipopolysaccharide (LPS), oncogenes. COX-2 is specially overexpressed in gastroenteric tumor, and one of the mechanism that COX-2 can promote carcinogenesis is that it inhibit tumor cell apoptosis. But there are few reports on their expression and their correlation in GBC. This study evaluated the roles of survivin, caspase-3 and COX-2 in GBC and their interaction in order to explain the mechanism of carcinogenesis of GBC, furtherly to provide theoretical foundation for prevention and clinical treatment. METHODS: The immunohistochemistry was used to detect the expression of survivin, caspase-3 and COX-2 in 49 specimens of GBCs,9 cases of gallbladder adenoma and 10 cases chronic caculous cholecystitis.RESULTS: Positive cytoplasmic immunoreactivity was detected in a proportion of 65.3% for survivin , 44.9% for caspase-3, and 75.5% for COX-2 in GBC, respectively. There was a significant difference in malignant lesion than in benign diseases. There was no significant association between the expression of survivin and patients'clinicopathological features, while the expression of caspase-3 was associated with differentiation. There was a relationship between COX-2 expression and the invasion depth, lymph node metastases and Nevin's staging. Furthermore, the expression of survivin correlated positively with COX-2 expression(r = 0.404,P = 0.004) and inversely with caspase-3(r = -0.373,P = 0.008),but no significant correlation was found between the expression of caspase-3 and COX-2 (r = -0.156,P = 0.284).CONCLUSION: The over-expression of survivin and COX-2 and descended expression of caspase-3 play a important role in the carcinogenesis and progression of GBC. Survivin and COX-2 may be identified as a potential therapeutic target in gallbladder carcinoma.