The Study Of Correlations Of Survivin, VEGF And Smac Expression And Clinicopathologic Characteristics In Primary And Metastatic Ovarian Carcinoma

Objective: To investgate the expression of Smac, VEGF and Survivin in primary and metastatic ovarian carcinoma and to explore their relationship with relevant clinical pathologic characteristics and prognosis, hoping to provide a theoretic basis for clinical diagnosis, treatment and predicting prognosis.Methods: The expression of Smac, Survivin and VEGF was detected by S-P immunohistochemical (IHC) stain in tissue samples from primary and metastatic ovarian carcinoma, benign epithelial ovarian tumor and normal ovarian tissues. The contents of Smac, VEGF and Survivin in ovarian carcinoma were quantitatively evaluated by flow cytometry (FCM). All data were analysized by SPSS 11.5 for Windows.Results: 1. The immunohistochemical staining results in primary ovarian carcinoma1.1 In primary ovarian carcinoma positive rate of Smac was 80.9%, respectively, the expression was significantly lower than that in benign ovarian tumor and normal ovarian tissues (P<0.01). In primary ovarian carcinoma, positive rate of nuclear and cytoplasmic Survivin were 72.4% and 87.2% respectively; the expression was significantly higher than those in benign ovarian tumor and normal ovarian tissues (P<0.05, P<0.01). In primary ovarian carcinoma, positive rate of VEGF was 91.5%, respectively, the results were significantly higher than that in benign ovarian tumor and normal ovarian tissues (P<0.05).1.2 In primary ovarian carcinoma, the expression of nuclear Survivin was correlated with age, divided by median age of 55, the positive rate of higher group (52.6%) was lower than that of lower group (85.7%) (P<0.05); the expression of cytoplasmic Survivin was positively correlated with clinical stage, the positive rate ofⅠ-Ⅱ(68.8%) was lower than that ofⅢ-Ⅳ(96.8%) (P<0.05); the expression of Smac was negatively correlated with clinical stage and differential degree (P<0.01, P<0.05),Ⅰ-Ⅱ(100%),Ⅲ-Ⅳ(71%), well and moderated differentiated group (96.2%), poorly differentiated group (61.9%). The expression of VEGF was positively correlated with age, the positive rate of higher group (78.9%) was lower than that of lower group (100%) (P<0.05).1.3 Spearman correlation analysis indicated that in primary ovarian carcinoma, the positive expression of nuclear Survivin was in positive correlation with that of cytoplasmic Survivin (P<0.01), those with expression of cytoplasmic Survivin were also nuclear positive. There was a negtive correlation between the expression of cytoplasmic Survivin and Smac (r=-0.312, P<0.05), while a positive correlation between the expression of cytoplasmic Survivin and VEGF (r=0.298, P<0.05). 1.4 The expression of proteins and prognosis: Patients with positive expression of cytoplasmic Survivin had worse overall survival (P<0.05); Patients with positive expression of cytoplasmic Smac had better overall survival (P<0.01). Multivariate analysis using Cox regression modal showed that only positive expression of 75% VEGF was the important independent prognostic factor for survival.2. The immunohistochemical staining results in metastatic ovarian carcinoma2.1 In metastatic ovarian carcinoma, positive rate of Smac was 77.4%, which was significantly lower than the rate in benign ovarian tumor and normal ovarian tissues (P<0.01). Positive rate of nuclear and cytoplasmic Survivin was 100% and 90.4% respectively, which were significantly higher than the rates in benign ovarian tumor and normal ovarian tissues (P<0.01). Positive rate of VEGF was 90.32%, which was significantly higher than the rate in benign ovarian tumor and normal ovarian tissues (P<0.01).2.2 In metastatic ovarian carcinoma, expression of cytoplasmic Survivin and VEGF were correlated with tumor size, positive rates in the cases with diameter below 5cm (66.7%) were significantly lower than those in the cases with diameter above 5cm (100%) (P<0.05); expression of Smac was correlated with differential degree which was significantly lower in well and moderately differentiated group (57.1%) than in poorly differentiated group (94.1%) (P<0.05). 2.3 There was a negtive correlation between the expression of Survivin and Smac (r=-0.373, P<0.05), while a positive correlation between cytoplasmic Survivin and VEGF (r=0.397, P<0.05).3. Results detected by FCM3.1 Relative expression of three proteins in tissues of carcinoma3.1.1 Survivin: In primary ovarian carcinoma, the value of FI in the clinical stage ofⅠ-Ⅱ(0.926±0.158) was significantly lower than that in the stage ofⅢ-Ⅳ(1.103±0.093) (P=0.025); In metastatic ovarian carcinoma, the value of FI in the cases with diameter below 5cm (1.038±0.049) was significantly lower than that in the cases with diameter above 5cm (1.155±0.080) (P=0.005).3.1.2 Smac: In primary ovarian carcinoma, the value of FI in well and moderately differentiated group (0.904±0.077) was significantly higher than that in poorly differentiated group (0.817±0.066) (P=0.021); In metastatic ovarian carcinoma, however, the value of FI in well and moderately differentiated group (0.777±0.091) was significantly lower than that in poorly differentiated group (0.876±0.031) (P=0.010).3.1.3 VEGF: In primary ovarian carcinoma, the value of FI in the clinical stage ofⅠ-Ⅱ(1.032±0.021) was significantly lower than that in the stage ofⅢ-Ⅳ(1.176±0.093) (P=0.045); In metastatic ovarian carcinoma, the value of FI in the cases with diameter below 5cm (1.061±0.107) was significantly lower than that in the cases with diameter above 5cm (1.180±0.083) (P=0.030).3.2 The comparison of three proteins among tissues of carcinoma, benign ovarian tumor and normal ovarian tissues: In primary and metastatic ovarian carcinoma, values of FI of Survivin, VEGF were significantly higher than those in both benign ovarian tumor and normal ovarian tissues, by contrast the value of Smac was significantly lower than that in both benign ovarian tumor and normal ovarian tissues.Conclusion:1 Expression of cytoplasmic Survivin and expression of cytoplasmic Smac may be used as important prognostic indicators.2 The expression of Smac was significantly lower in epithelial ovarian carcinoma than that in benign ovarian tumor and normal ovarian tissues, indicates that lower expression of Smac plays a very important role in the occurrence and development of carcinoma.3 The expression of Survivin was significantly higher in epithelial ovarian carcinoma than that in benign ovarian tumor and normal ovarian tissues, higher expression indicating as inhibitor of apoptosis, Survivin also plays a very important role in the occurrence and development of ovarian carcinoma.4 The difference between the expression of nuclear Survivin and cytoplasmic Survivin further indicated that Survivin is a nuclear-cytoplasmic shuttling protein.5 The expression of cytoplasmic Survivin was negatively correlated with Smac expression, while positively correlated with VEGF. The fact indicated Survivin and Smac might play opposite role in occurrence, development and metastasis of epithelial ovarian carcinoma.