The Expression And Significance Of P-stat3 And Ki67 In Epithelial Ovarian Tumor

Background and objectiveOvarian cancer is the most common cause of mortality among the genital organ malignancies and epithelial ovarian cancer comprises of 80%of them.Due to lack proper screening tools,early diagnosis of ovarian cancer is difficult and also the symptoms are often vague and nonspecific.Because of its insidious onset,ovarian cancer patients are often diagnosed at advanced stage.Though new surgical techniques and new chemotherapeutic drugs have emerged in recent years,the prognosis is very poor with 5-years survival rate of only about 30%.It is multi-stage process and more than one gene may be involved in the occurrence and development of ovarian cancer.The development of molecular biology,oncogenes and their products has provided scientific and objective information for the clinical detection of tumor pathogenesis,assessment of metastasis and prognosis.Therefore,further study of the biological behavior,factors and related mechanisms of malignant ovarian cancer will be more effective for early diagnosis,evaluation methods and indicators of prognosis.As it has theoretical and practical significance,it is difficult but important to explore more effective blocker,control of tumor proliferation,metastasis,and tumor biology.Signal transducer and activator of transcription 3(STAT3) signal transduction pathway directly affect cell proliferation,differentiation and apoptosis.The pathway activation leading to abnormal cell proliferation and malignant transformation is defined as oncogene.Elements STAT3 is mainly activated through tyrosine phosphorylation by JAK kinase activation.STAT3 monomer through the SH2 domain and another molecule STAT3 phosphorylation of tyrosine residues to form dimers into the nucleus interactions regulate target gene transcription.STAT3 is the focus of convergence of EGFR,IL-6/JAK,Src and other tyrosine kinase signal carcinogenicity channel and is over-activated in a variety of tumor cells and tissues.Upstream tyrosine kinases such as JAK,Src and EGFR inhibitors have been developed,some have entered the clinical trial stages and the application of tyrosine kinase inhibitors in the treatment of ovarian cancer research clinical trials has begun As cell proliferation marker Ki67 antigen in recent years has been widely used to study the biological behavior of tumors to determine the harmfulness of the tumor is the most promising markers of cell proliferation.Ki76 is an important p-STAT3 signaling molecules downstream.At the same time to study and learn more about the relationship between STAT3 and ovarian cancer cell proliferation.In this study,we investigated the expression of p-STAT3 protein and Ki76 protein in normal ovary,benign epithelial ovarian tumor and malignant ovarian tumor by using immunohistochemistry method and analyzed the relationship of p-STAT3 and Ki76.The purpose was to explore the effect and meaning.As a consequence,the results would provide some theoretical grounds to the early diagnosis and treatment of malignant ovarian tumor.Methods1.Sampling:90 operable cases were selected from the Third Affiliated Hospital of Zhengzhou University and Henan Cancer Hospital since July 2007～May 2008.The age of patients ranged from 32 to 68,including the malignant ovarian tumor(n=40),benign epithelial ovarian tumor(n = 30) and normal ovary tissue(n=20).All diagnoses of specimens were confirmed by pathology.According to clinical data,histological grate:19 cases of well-differentiated,21 cases of poorly differentiated;lymphatic metastasis:12 of positive,28 of negative;clinical stage:Ⅰ:9,Ⅱ:10,Ⅲ:15,Ⅳ:6.No any drug was taken preoperatively,also no radiotherapy chemotherapy immunotherapy.2.Method:To detect the expression of p-STAT3 and Ki67 in normal ovary,benign epithelial ovarian tumor and malignant ovarian tumor by immunohistochemistry.3.Assessment:According to staining intensity and double number of positive cells in semi-quantitative scoring points.4.Statistic analysis:The data were recorded and analyzed by using SPSS11.5 package,and were compared in two groups throughχ~2 analysis.The dependability of two indexes deploy Spearman's rank-order Correlation.Significance level isα= 0.05.Results1.The expression of p-STAT3 protein is mainly located at the nucleus or cytoplasm in the normal ovarian tissue and the benign epithelial ovarian tumor tissue; the positive expression of p-STAT3 protein in the malignant ovarian mainly in the nucleus.The positive expression rates of p-STAT3 in the normal ovarian tissue,the benign epithelial ovarian tumor and the malignant ovarian tumor was 20.00%,30.00% and 80.00%(χ~2=20.000,P＜0.05;χ~2= 17.662,P＜0.05) respectively.The expression of p-STAT3 was significant between the three groups.In the malignant ovarian tumor, there was significant difference in the expression of p-STAT3 protein betweenⅠ-Ⅱperiod andⅢ-Ⅳ,as well as in the classification of different organizations and in the lymph node metastasis.There was no significant difference among the age groups and pathological types.2.The expression of Ki67 protein is present mainly in the nucleus.In the normal ovarian tissue,benign epithelial ovarian tumor and the malignant ovarian tumor,the positive expression rate of Ki67 was 15.00%,30.00%and 77.50%respectively.The difference in expression of Ki67 in the three groups was statistically significant(χ~2= 26.575,P＜0.001).Similarly in the malignant ovarian tumor,there was significant difference in the expression of Ki67 protein betweenⅠ-Ⅱperiod andⅢ-Ⅳas well as in the classification of different organizations.There was no significant difference in with or without lymph node metastasis,among age groups and pathological types.3.To analyze the correlation expression of p-STAT3 protein and Ki67 protein in the malignant ovarian tumor,the expression of p-STAT3 protein and Ki67 protein was positively correlated(r=0.813,P＜0.001).Conclusion1.The higher expression of p-STAT3 protein could lead to out-of-control cell proliferation,malignant transformation,occurrence promotion and development of malignant ovarian tumors.2.The expression of p-STAT3 protein and Ki67 protein was positively correlated in the malignant ovarian tumor.These proteins together could serve as an indicator for malignant proliferation of ovarian cancer and also as a marker for abnormal STAT3 signaling pathway,leading to excessive proliferation of tumor cells.