Expression Of Epha2 And Cyclind1 In Osteosarcoma And Clinical Significance

Receptor tyrosine kinases,RTKs plays the important roles during the process of cell growth and differentiation,participating in embryonic development,cell growth, invasion and metastasis and so on.As a member of the biggest subgroup erythropoietin producing hepatoma cell line receptor kinase family of PTK,EphA2 expresses lower in mature endothelial cell,combined with cellular surface embryonic plant Ephrin(EFN) A1-5,which results in phosphorylation of EphA2 receptor, moreover through downstream signals regulating cell normal growgh,development and so on,promoting personal degradation of EphA2 receptor at the same time.Thus in tumor cells,EphA2 is expressing higher increasingly as unphosphorylation.The research indicated that EphA2 had potential roles during the process of tumor cell growth,existence,migration and tumor neovascularization.At the same time,EphA2 is expressing higher increasingly in many human malignant tumors for example breast cancer,melanocytoma,esophageal carcinoma,non-small cell carcinoma,cancer of colon,prostatic carcinoma and ovarian cancer and so on,and its expression levels are relative to progression and cellular malignant degree of tumor.CyclinD1 is a regulatory protein of G1 stage to S stage of cell cycle,combining with Cyclin Dependent Kinase completely,making Rb protein phosphorylation due to the roles of CDK4.Rb of low phosphorylation combines and inhibits transcription factor,which activates some genes,promoting entering S stage of cell.Rb of low phosphorylation stimulates synthesis,transcription and activation of CyclinD1,and leading to phosphorylation of Rb,thus forming a feedback loop regulates the expression of CyclinD1 in G1 advanced stage.Overexpressions of CyclinD1 causes regulatory dysfunction of cell cycle,therefore generating tumor.The research confirmed that CyclinD1 expesses lower or not in normal tussues,thus there are overexpressions in many malignant tumors for example mantle cell lymphoma,prostatic carcinoma, breast cancer and squamous carcinoma of head and neck and so on,having importantly clinical significances in some aspects of predicting tumor progressions and guiding patient prognosis.Osteosarcoma is one of the most frequent malignant bone tumors of children and teenage,having highly malignant degree.The documents indicated that the dead on account of local infiltration and pulmonary metastasis ocuupided 90%of total death of osteosarcoma.Therefore,predicting efficiently and healing infiltration and metastasis of osteosarcoma is the key of prolonging life of patients.Detecting the expressions of EphA2 and CyclinD1in osteosarcoma,and its clinical significance,to this date domestic and foreign documents havenot reports.Our research adopts immunohistochemistry sp method,observing the expressions of EphA2 and CyclinD1 protein in osteosarcoma tissues of 50 cases,osteochondroma tissues of 20 cases and normal bone tissues of 20 cases,analyzing the relationship of between combined expressions and development,invasion and metastasis of osteosarcoma,looking for latest molecular targets of early detecting of osteosarcoma and controlling infiltration and metastasis of osteosarcoma.Methods1.Applicating the methods of immunohistochemistry SP to detect the expression of EphA2 and CyclinD1 in the 50 cases of osteosarcoma tissues,20 cases of osteochondroma tissues and 20 cases of normal bone tissues respectively.2.Statistical analysis:All the dates were analyzed by SPSS 11.0 statistical package,the count information calculated the positive rate,The comparison of positive rates uses the Chi-square;The relation of two variable are analyzed by the spearman level correlation analysis.The level of significant difference isα=0.05.Results1.Immunohistochemical results indicated:the positive expression rates of EphA2 protein in normal bone tissues are 0.00%(0/20);The positive expression rates of EphA2 protein in osteochondroma tissues are 0.00%(0/20);The positive expression rates of EphA2 protein in osteosarcoma tissues are 78.00%(39/50),the positive expression rates of EphA2 protein in osteosarcoma tissues are compared with those in the propotional osteochondroma tissues and normal bone tissues from each other, There is stastital significance(P＜0.05).2.Immunohistochemical results indicated:the positive expression rates of CyclinD1 protein in normal bone tissues are 0.00%(0/20);The positive expression rates of CyclinD1 protein in osteochondroma tissues are 0.00%(0/20);The positive expression rates of CyclinD1 protein in osteosarcoma tissues are 78.00%(39/50),the positive expression rates of CyclinD1 protein in osteosarcoma tissues are compared with those in the propotional osteochondroma tissues and normal bone tissues from each other,There is stastital significance(P＜0.05).3.The positive expression rates of EphA2 protein of male and female in osteosarcoma tissues are 80.00%(24/30),75.00%(15/20) respectively,there is no significance between both(P＞0.05);The positive expression rates of EphA2 protein in osteosarcoma tissues with Osteoblast,fibroblast,Chondroblast and other are 75.00%(15/20),86.67%(13/15),70.00%(7/10),80.00%(4/5)respectively,there is no significance between four kinds of pathological types(P＞0.05).4.The positive expression rates of CyclinD1 protein of male and female in osteosarcoma tissues are 73.33%(22/30),65.00%(13/20) respectively,there is no significance between both(P＞0.05);The positive expression rates of CyclinD1 protein in osteosarcoma tissues with Osteoblast,fibroblast,Chondroblast and other are 65.00%(13/20),80.00%(12/15),70.00%(7/10) and 60.00%(3/5) respectively,there is no significance between four kinds of pathological types(P＞0.05).5.The positive expression rates of EphA2 protein in osteosarcoma tissues withⅠperiod,Ⅱperiod andⅢperiod are 40.00%(4/10),72.22%(13/18) and 100.00%(22/22) respectively,the positive expressions rates of EphA2 protein in osteosarcoma tissues withⅢperiod are higher than those inⅠperiod andⅡperiod, There is stastital significance between different clinical stages(P＜0.05).6.The positive expression rates of CyclinD1 protein in osteosarcoma tissues withⅠperiod,Ⅱperiod andⅢperiod are 40.00%(4/10),72.22%(13/18) and 100.00%(22/22) respectively,the positive expressions rates of CyclinD1 protein in osteosarcoma tissues withⅢperiod are higher than those inⅠperiod andⅡperiod, There is stastital significance between different clinical stages(P＜0.05).7.The positive expression rates of EphA2 protein in osteosarcoma tissues with pulmonary metastasis are 100.00%(20/20),the positive expression rates of EphA2 protein in osteosarcoma tissues with nonpulmonary metastasis are 60.00%(18/30), There is stastital significance between two groups(P＜0.05).8.The positive expression rates of CyclinD1 protein in osteosarcoma tissues with pulmonary metastasis are 100.00%(20/20),the positive expression rates of CyclinD1 protein in osteosarcoma tissues with nonpulmonary metastasis are 50.00%(15/30), There is stastital significance between two groups(P＜0.05).9.The relativity of the expression of EphA2 and CyclinD1 was analysized by statistics,Results showed that there is a positive correlation between them(P＜0.01).Conclusions1.The positive expression rates of EphA2 protein in osteosarcoma tissues withⅠperiod,Ⅱperiod andⅢperiod are different,the positive expression rates of EphA2 protein in osteosarcoma tissues are high in turn with lowing of differentiation degree,the positive expression rate of EphA2 protein in osteosarcoma tissues withⅢperiod are compared with those inⅠperiod andⅡperiod from each other,It indicated that the expressions of EphA2 protein could be associated with progression of osteosarcoma.2.The positive expression rates of CyclinD1 protein in osteosarcoma tissues withⅠperiod,Ⅱperiod andⅢperiod are different,the positive expression rates of CyclinD1 protein in osteosarcoma tissues are high in turn with lowing of differentiation degree,the positive expression rate of CyclinD1 protein in osteosarcoma tissues withⅢperiod are compared with those inⅠperiod andⅡperiod from each other,It indicated that the expressions of CyclinD1 protein could be associated with progression of osteosarcoma.3.The relativity of the expression of EphA2 and CyclinD1 protein was analysized by statistics,Results showed relative and they played synergistic effect during the process of occurrence and development and infiltration,metastasisof osteosarcoma.