The Constitutive Activation Of Stat3 Signaling Pathway And Significance In Epithelial Ovarian Carcinoma

Objective:To investigate the expressions of Stat3 and p-Stat3 in different epithelial ovarian tissues and explore the role of constitutive activation of Stat3 signaling pathway in the pathogenesis of epithelial ovarian carcinoma(EOC).To investigate the relationship between expressions of Stat3 or p-Stat3 in EOC and clinical pathological parameters or prognosis and explore the role of constitutive activation of Stat3 signaling pathway in the invasion and metastasis of EOC.To investigate the expressions of Survivin or VEGF protein in EOC and their correlation with the expressions of Stat3 or p-Stat3 and explore the possible mechanism of Stat3 signaling pathway in EOC.Methods:50 case of EOC visited the Obstetrics and Gynecology Department of Second Shanxi Medical University were chosen as research objects,and 20 cases of benign ovarian tumors and 20 cases of normal ovarian tissues were chosen as controls,and then all clinical pathological data of research objects were collected.The expressions of Stat3,p-Stat3 and Survivin,VEGF were detected by immunohistochemical method.The survival status and time of all EOC patients since surgery to the date of March 8,2007 were followed up.All the data was organized and analyzed by SPSS 13.0 statastical software.The differences of expressions of Stat3,p-Stat3 and Survivin,VEGF protein in EOC and controls were analyzed by x~2 test;the relationships between the expressions of Stat3,p-Stat3 protein and various clinical pathological parameters were analyzed by Spearman rank correlation;and the relationships between their expressions and the prognosis of patients were analyzed by Kaplan-Meier method.Results:1.Stat3 protein was overexpressed and overactivated in EOC tissues1.1 The positive expressions of Stat3 were located both in cytoplasm and in cell nucleus, but mainly in the former.The positive ratio of Stat3 expression in the EOC tissues was 88%, which was significantly higher than those in normal ovarian epithelial tissues 30%(P＜0.0125) and those in benign ovarian tumor tissues 45%(P＜0.0125).1.2 The p-Stat3 is the active form of Stat3 protein,and the extent of expressions of p-Stat3 means the degree of the activation of Stat3 signaling pathway.The positive staining mainly located in cell nucleus.The positive ratio of p-Stat3 expression in the EOC tissues was 58%, which was significantly higher than those in normal ovarian epithelial tissues 15%(P＜0.0125) and those in benign ovarian tumor tissues 20%(P＜0.0125). 1.3 The expressions of Stat3 protein were significantly correlated with the expressions of p-Stat3 protein(P＜0.01).2.The relationship between the expressions of Stat3 or p-Stat3 protein and the Clinical pathological parameters in EOC2.1 It was not observed that the expression of Stat3 protein was related to age,the maximum diameter of the primary focus and lymph node metastasis(P＞0.05),but the positive ratio of Stat3 exprssion in stages ofⅢ+Ⅳ(96.9%) was significantly higher than those in stages ofⅠ+Ⅱ(72.2%)(P＜0.05).At the same time,the expressions of Stat3 were gradually increased with the reduction of differentiation(P＜0.05).2.2 It was not observed that the expressions of p-Stat3 protein were related to age and the maximum diameter of the primary focus(P＞0.05),but the expressions of Stat3 were significantly correlated with the disease stage,the differentiation and lymph node metastasis.Along with the higher clinical stage(P＜0.05),the inferior differentiation(P＜0.01) and the regional lymph node metastasis(P＜0.01),the expressions of p-Stat3 were gradually increased.3.The relationship between expressions of Stat3 or p-Stat3 and prognosis of EOC casesNo correlation was observed between the expressions of Stat3 and prognosis of EOC (P＞0.05),but the expressions of p-Stat3 protein were negatively correlated with the prognosis of the EOC patients(P＜0.01),which means the positive staining of p-Stat3 protein may forecast an inferior prognosis.4.The expressions of Survivin,VEGF in EOC and the relationship between the expressions of Survivin,VEGF and Stat3,p-Stat3 protein4.1 The positive expressions of Survivin were located mainly in cytoplasm.No Survivin protein was expressed in normal ovarian tissues.The positive ratio of Survivin expression in the EOC tissues was 72%,which was significantly higher than those in benign ovarian tumor tissues 20%(P＜0.0125).4.2 The positive expressions of VEGF were located in cytoplasm.The positive ratio of VEGF expression in the EOC tissues was 82%,which was significantly higher than those in benign ovarian tumor tissues 30%(P＜0.0125) and those in normal ovarian epithelial tissues 45% (P＜0.0125).4.3 The expressions of Stat3 or p-Stat3 protein were significantly correlated with the expressions of Survivin or VEGF protein(P＜0.01).But there was no significant correlation between expressions of Survivin and VEGF protein(P＞0.05).Conclusion:1.Overexpression and overactivation of Stat3 was found in EOC tissuses,suggesting that the constitutive activation of Stat3 signaling pathway maybe involved in the tumorgenesis of EOC.2.The expressions of Stat3 protein were correlated with clinical stage and histological differentiation and the expressions of p-Stat3 protein were correlated with clinical stage,lymph node metastasis and histological differentiation,suggesting the constitutive activation of Stat3 signaling pathway may take an important role in the invasion and metastasis of EOC.3.The positive staining of p-Stat3 protein was correlated with a poor prognosis,suggesting that blocking the constitutive activation of Stat3 signaling pathway may delay the progress of EOC and improve the prognosis of the patients.4.The mechanism of Stat3 signaling pathway in EOC maybe achieved by upregulating expressions of Survivin and VEGF gene.