Study On The Expression Of Endostatin In Cervical Lesions And Its Relationship With The Microvessel Density

Cervical cancer is one of the most common malignant tumors in women.According to the report 500,000 people suffered from cervical cancer in the World every year only a little less than who got breast cancer. New incident patients of cervical cancer every year is 150,000 in China which is the first in the world.Cervical intraepithelial neoplasia is a precancerous cervical lesions.It reflect the progressive and continuous process of cervical lesions.We can divide cervical intraepithelial neoplasia into CINⅠ,CINⅡand CINⅢby pathological levels.Each has respectively 15%,30% and 45% of the risk for progressing into cervical cancer.Angiogenesis plays an important role in the progress of cervical lesions.In the course of tumor growth,there are two stages—prevascular phase and vascular phase.The transformation process of two stages is called angiogenic switch. Prevascular phase is the early stage of the development of tumor,in which there is almost no localized neovascularization.Proliferation and mortality rates of tumor cells are also similar.The volume of tumor is hard to over 1～2mm3,and metastasis is also very rare.Vascular phase is characterized by a large number of local tumor angiogenesis,exponential growth and infiltration of tumors. Tumor cells can easily penetrate the vascular wall and disseminate away.Neovascular is highly permeable and basement membrane of neovascular is incomplete.Plasminogen kinase and collagenase secreted by endothelial cells play an important part in this activity. The reasons of local angiogenic switch is that the balance is broken between inhibitory factors and stimulating factors. Endostatin is a protein which hydrolysis from the end of the carboxyl-terminal fragment of extracellular collagenⅩⅧ.It contains 184 amino acids and molecular weight is 20 ku.In 1971, Folkman proposed a point of view for the first time that tumor growth depends on angiogenesis.The role of angiogenesis in the process of cancer incidence and anti-tumor therapeutic effect of antiangiogenesis attract more and more scholars'intereste.The reaserchers have made a great progress. The expression of Endostatin in cervical lesions but has yet to see in the relevant literatures.Our study by analyzing the expression of Endotatin in cervical lesions and its relationship with microvessel density will reveal preliminarily the relations between the expression of Endostatin and angiogenesis.Our study is of great significance in understanding the mechanism of the incidence and development in cervical lesions.What's more,our study lays the theoretical foundation for clinical application of Endostatin and anti-angiogenesis treatment of cervical lesions.Objective: To study the expression and distribution of Endostatin and microvessel density in normal cervix,cervical intraepithelial neoplasia and cervical cancer,and to analyze their correlations.Methods: A total of 75 cervical specimens were divided into 5 groups,each comprising of 15 from normal epithelia,CINI,CINⅡ,CINⅢto cervical cancer.Immunohistochemical staining technique was used to detect the expression intensity of endostatin.Vascular endothelial cells were marked by CD34 monoclonal antibody to calculate microvessel density and quantify the extent of neovascularization.Results: (1) Endostatin expressed in all groups, Endostatin mainly located in the dysplasia cells and the cytoplasm of tumor cells. Microvascular endothelial cells and inflammatory cells of mesenchymal showed moderate expression.The expression of endostatin increased with the progression of cervical lesions.There were significant differences between the control group and the study groups(P<0.05).The differences within the research groups were significant(P<0.05)except CINI and CINⅡ(P=0.448).(2) CD34 staining of microvessel density was positive in the microvascular endothelial cells which mainly distributed below the epithelial basement membrane. Microvessel was rich,irregular and disorder in cervical cancer,which mainly distributed in the edge of cancer nest.The expression of microvessel density increased with the progression of cervical lesions.There were significant differences between the control group and the study groups(P<0.05).The differences within the study groups were also significant(P<0.05).(3)Pearson correlation analysis showed that the expression of Endostatin and MVD in cervical lesions were significantly correlated(r=0.831,P<0.01).Conclusion:(1)Angiogenesis is existed from cervical intraepithelial neoplasia to invasive cervical cancer.(2)The expression of Endostatin and MVD increase with the progression of cervical lesions.(3)The expression of Endostatin is related to the angiogenesis in cervical lesions.Endostatin involves in the development process of cervical lesions.(4)Endostatin provides a new strategy for anti-angiogenesis therapy of cervical lesions.