Expression And Significance Of AnnexinⅡ,caspase-3 And Survivin In Ovarian Carcinoma

Background and objective:Ovarian carcinoma is the most common cause of death in gynecological malignancies. For its growth is Rapid, the five-year survival rate is low. It is a serious threat to the health of women. It is generally accepted that the occurrence and development are closely related to the changes of tumor cell biology behavior. Disorder of apoptosis mechanisms is a common cause of tumor occurrence. In recent years, research of carcinoma apoptosis has become a hot spot.Annexin II is one of Ca²⁺-and phospholipids-binding proteins. It's encoding gene is located on chromosome 15q21-q22. The study found that Annexin II protein plays an important role in the cell cycle. In recent years, the over-expression of Annexin II has been observed in Colorectal carcinoma,Primary renal cell carcinoma,Hematologic malignancies. But another study showed that Annexin II protein expression is decreased From normal epithelium, intraepithelial neoplasia to carcinoma tissue. Therefore, Annexin II protein expression and the relationship between malignant tumors require further study. In addition, it is reported in the literature, Annexin II involved in P53-mediated apoptosis.caspase-3 is an important member of the apoptotic protease family, Caspase family plays a very important role in mediating apoptosis, in which caspase-3 is the key elements, In the early stages of apoptosis, it is activated, the activation of Caspase-3 is made of two major subunits (17KD) and two small subunit (12KD).they cracked the corresponding substrate in cytoplasm and nucleus, eventually leading to cell apoptosis.Survivn is an apoptosis suppressor gene, Survivn can block the mitochondrial pathway and death receptor pathway which were two main pathways of apoptosis through direct inhibition of caspase-3, caspase-7, or interfere with the activity of caspase-9.it plays a role in apoptosis inhibition ultimately.To explore the expression of Annexin II, caspase-3, surviving proteins in ovarian benign tumor and ovarian carcinoma tissues, and analyse their relationships between their expression and the ovarian carcinoma's clinical pathological characters In this study we study the role of Annexin II proteins in the development of Ovarian carcinoma, and its relation with caspase-3, survivin proteins in the development of Ovarian carcinoma by Immunohistochemistry. We will provide a new proof and effective indicators for ovarian carcinoma diagnosis and treatment.Materials and methods:52 cases of Ovarian Carcinoma were collected in the First Affiliated Hospital, Zhengzhou University. 40 cases are serous carcinoma, 12 cases are mucinous carcinoma. All the specimens are graded according to WHO pathology standard. 14 cases are grade1(G₁),16 cases are grade2(G₂), 22 cases are grade3(G₃). All the specimens are staged according to FIGO of 2000 year. 8 cases are stage I, 14cases are stage II, 27 cases are stageIII, 3 cases are stageIV. 28 cases had the lymph node metastasis, 24 cases non-lymph node metastasis. Other 18 cases are benign tumor of the ovary. The expressions of Annexin II,caspase-3 and surviving protein were detected in 52 cases of ovarian carcinoma and 18 benign tumor of the ovary by immunohistochemistry. All the data were analyzed by SPSS10.0 statistical package. The comparison of positive rate uses the Chi-square test; the relation of two variables is analyzed by Spearman's correlation analysis. It was significant difference when P<0.05.Results:1. The positive rates of expression of Annexin II protein in benign tumor of the ovary were 44.45%(8/18), and in ovarian carcinoma were 80.77%(42/52). There was a significant difference between ovarian carcinoma and benign tumor of the ovary (P<0.05). The positive rates of expression of Annexin II protein in serous ovarian carcinoma were 80.0%(32/40)and in mucinous ovarian carcinoma were 83.33% (10/12), there was no significant difference between them (P>0.05) . The positive rates of expression of Annexin II protein in grade G₁, G₂ and G₃ were 71.43% (10/14), 87.50% (14/16)and 81.82% (18/22),respectively. there was no significant difference among them (P>0.05) . The positive rates of expression of Annexin II protein on the stage I and II, stageIII and IV were 54.55% (12/22) and 100.0%(30/30)respectively, There was a significant difference between them(P<0.05). The positive rate of expression of Annexin II protein in the group without lymph node metastasis was 67.86% (19/28). While in the group with lymph node metastasis, it was 95.83% (23/24), There was a significant difference between them (P<0.05).2. The positive rates of expression of caspase-3 protein in benign tumor of the ovary were 94.44% (17/18), and in ovarian carcinoma were 48.08%(25/52). There was a significant difference between ovarian carcinoma and benign tumor of the ovary (P<0.05). The positive rates of expression of caspase-3 protein in serous ovarian carcinoma were 47.5%(19/40)and in mucinous ovarian carcinoma were 50.0%(6/12), there was no significant difference between them (P>0.05) . The positive rates of expression of caspase-3 protein in grade G₁, G₂ and G₃ were 42.86% (6/14), 56.25% (9/16) and 45.45%(10/22),respectively. there was no significant difference among them (P>0.05) . The positive rates of expression of caspase-3 protein on the stage I and II, stageIII and IV were 77.27%(17/22) and 26.67%(8/30)respectively, there was no significant difference between them (P<0.05) . The positive rate of expression of caspase-3 protein in the group without lymph node metastasis was 50.0% (14/28). While in the group with lymph node metastasis, it was 45.83%(11/24), there was no significant difference between them (P>0.05) .3. The positive rates of expression of survivin protein in benign tumor of the ovary were 22.22% (4/18), and in ovarian carcinoma were 61.54% (32/52). There was a significant difference between ovarian carcinoma and benign tumor of the ovary (P<0.05). The positive rates of expression of survivin protein in serous ovarian carcinoma were62.5%(25/40)and in mucinous ovarian carcinoma were 58.33%(7/12), there was no significant difference between them (P>0.05) . The positive rates of expression of survivin protein in grade G₁, G₂ and G₃ were 28.57% (4/14), 56.25% (9/16) and 86.36% (19/22), respectively, there was a significant difference among them (P<0.05).The positive rates of expression of survivin protein on the stage I and II, stageIII and IV were 40.91% (9/22) and 76.67%(23/30)respectively, There was a significant difference between them(P<0.05). The positive rate of expression of survivin protein in the group without lymph node metastasis was 39.29% (11/28), While in the group with lymph node metastasis, it was 87.50% (21/24). There was a significant difference between them (P<0.05).Conclusions:1 .By detecting the expression of Annexin II and survivin protein in benign ovarian epithelial tumors and ovarian carcinoma tissues, we found that the rate of the expression of Annexin II and survivin protein in benign ovarian carcinoma are higher than that in ovarian epithelial tumors, which indicate that the expression of Annexin II and survivin protein may be correlated with the carcinogenesis of ovarian carcinoma, we found that the rate of the expression of caspase-3 protein in ovarian carcinoma are lower than that in benign ovarian epithelial tumors, which indicate that the low expression of caspase-3 protein may be related to the occurrence of ovarian carcinoma.2.Annexin II protein positive expression rate has no relation with the histological type and histological grade of ovarian carcinoma, and has relation with FIGO stage and lymph node metastasis of ovarian carcinoma, which suggest that the expression of Annexin II protein can promote the development and metastasis of ovarian carcinoma.3. Caspase-3 protein positive expression rate has no relation with the histological type,histological grade,and lymph node metastasis of ovarian carcinoma. but it has relation with the FIGO stage of ovarian carcinoma.4.Survivin protein positive expression rate has no relation with the histological type of ovarian carcinoma while it has relation with histological grade,FIGO stage and lymph node metastasis of ovarian carcinoma. Which suggest that the expression of survivin protein can promote the development and metastasis of ovarian carcinoma.5. The expression of Annexin II protein was positive correlated with survivin protein while it was negative correlated with caspase-3 protein, the expression of Annexin II and survivin protein may be directly or indirectly inhibit caspase-3 protein activity and block the process of apoptosis therefore leading to the occurrence and development of ovarian carcinoma.