| Objective: Smac protein (the second mitochodria-derived activator of caspase) is a proapoptosis protein releasing from mitochondrion, which induces cell apoptosis by relieving the inhibition of IAP(inhibitor of apoptosis proteins). IAP bands with caspase(Cysteine aspartic acic specific protease). Smac protein is the first mammalian protein that can inhibit IAP by direct binding. Survivin protein is a member of IAP, which inhibits apoptosis by directly banding with caspase-3 and caspase-7. Survivin protein is strictly expressed in G/M phase during mitosis, and it is required for apoptosis inhibition, which may provide a selective cytoprotective mechanism at cell division, thus to promote cell division and proliferation. Survivin is the most powerful inhibitor of apoptosis. Survivin protein is expressed in many tumors, and its high expression associates with poor prognosis. In this study we detected the expression of Smac protein and Survivin protein in Esophageal Squamous Carcinoma by immunohistochemistry, and investigate the prognostic significance in Esophageal Squamous Carcinoma.Methods: Esophageal Squamous Carcinoma paraffin block specimens with full clinicopathological data were selected and confirmed by the postoperative pathologic diagnosis. There were 49 men and 25 women, aged from 40-77 years old, with mean age of 56.1 years old. According to the standard of TNM staging(UICC), 19 cases belong to T1 stage, 23 cases belong to T2 stage, 32 cases belong to T3 stage, in addition, 35 cases belong to N0 stage, 39 cases belong to N1 stage. All specimens were divided into three groups, according to postoperative life span. Thirty cases of apocarcinoma esophageal tissue were studied also. Specimens were cut into 4μm paraffin slices. Immunohistochemical staining for Smac protein and Survivin protein were performed. All data were correspondingly tested byχ2-test , rank sum test, Spearman rank correlation test, survival analysis(Kaplan-Meier method). P<0.05 was considered statistical significance. Then analyzed the expression of Smac protein and Survivin protein in esophageal squamous carcinoma, and investigated the prognostic significance.Results: 1 The expression of Smac protein and Survivin protein in esophageal squamous carcinoma and apocarcinoma esophageal tissue: The Smac protein positive expression rate in esophageal squamous carcinoma was 75.7%(56/74), the positive expression rate in apocarcinoma esophageal tissue was 96.7%(29/30). The difference was significant (P=0.012, P<0.05). The Survivin protein positive expression rate in esophageal squamous carcinoma was 68.9%(51/74), the positive expression rate in apocarcinoma esophageal tissue was 6.7%(2/30). The difference was significant(P<0.001). 2 The expression of Smac protein and Survivin protein in different survival group of esophageal squamous carcinoma: Smac protein presented high expression in long-term survival group, and low expression in short-term survival group, The difference was significant (P=0.002, P<0.05). Survivin protein presented high expression in short-term survival group, and low expression in long-term survival group, The difference was significant(P<0.001). 3 The relationship between the expression of Smac protein and Survivin protein in esophageal squamous carcinoma and clinocopatholonical characteristics: No correlation was observed between expression intensity of Smac protein and Survivin protein and some clinocopatholonical characteristics(age, gender, location). The expression of Smac protein and Survivin protein in esophageal squamous carcinoma was related to the infiltrating degrees, but the difference was not significant (P>0.05). There was association between the expression of Smac protein and Survivin protein in esophageal squamous carcinoma and lymph node metastasi or not, the difference was significant (P<0.05). 4 The correlation between the expression of Smac protein and Survivin protein in esophageal squamous carcinoma: When Smac protein presented high expression, Survivin protein often presented low expression; When Smac protein presented low expression, Survivin protein often presented high expression. There was a negitive correlation between the expression of Survivin and Smac in esophageal squamous carcinoma (r=-0.288, P<0.05). 5 The relationship between the expression of Smac protein and Survivin protein in esophageal squamous carcinoma and the postoperative accumulative survival rate. The patients whose smac protein presented high expression, their postoperative accumulative survival rate was high. The patients whose Survivin protein presented high expression, their postoperative accumulative survival rate was low.Conclusion: 1 The expression of Smac protein in esophageal squamous carcinoma was obviously lower than that in apocarcinoma esophageal tissue. In contrast, Survivin protein expressed higher in esophageal squamous carcinoma than that in apocarcinoma esophageal tissue. Their difference were significant (P<0.05). These indicate that low expression of Smac and high expression of Survivin promote the genesis and development of esophageal squamous carcinoma. 2 No correlation was observed between expression intensity of Smac protein and Survivin protein and some clinocopatholonical characteristics(age, gender, location). The expression of Smac protein and Survivin protein in esophageal squamous carcinoma was related to the infiltrating degrees, but the difference was not significant(P>0.05). There was association between the expression of Smac protein and Survivin protein in esophageal squamous carcinoma and lymph node metastasi or not, the difference was significant(P<0.05). These indicate that Smac protein and Survivin protein have relations with lymph node metastasi, and participate aversion of esophageal squamous carcinoma. 3 There was a negitive correlation between the expression of Smac protein and Survivin protein in esophageal squamous carcinoma (r=-0.288, P<0.05). It suggested that Smac and Survivin play antagonistic roles in cancer cell apoptosis. Decreasing the expression of Smac might indirectly or directly cause Survivin over-express. And the over-expression of Survivin inhibits cell apoptosis and promotes aberrant proliferation and malignant transformation of the cells. The relationship between Smac protein and Survivin protein may play a central role in esophageal squamous carcinoma. 4 The patients whose smac protein presented high expression, their postoperative life span was long , and their postoperative accumulative survival rate was high. The patients whose Survivin protein presented high expression, their postoperative life span was short ,and their postoperative accumulative survival rate was low. These indicate that Smac protein and Survivin protein are important index that judges the prognosis of esophageal squamous carcinoma.
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