| Background and ObjectiveCervical cancer is a malignant tumor that occurs at the junction of the cervical squamous epithelium and columnar epithelial cells in the cervical tube. It is one of the most common malignancy of women, the incidence of second place in the world, the rate of suffering from it is close to breast cancer. Therefore, it is a serious threat to women's health and life.More and more reports show that inflammation of the body is the primary inducement in the development of tumor. However, not all of the inflammation will develop into cancer. The cause of this event closes to immune regulation of one body and the microenvironment changes of the cervix. An epidemiologic study shows that above 99% of cervical cancer is associated with High-risk human papilloma virus (HPV) infection. That is, the persistent infection of HPV can destroy the cervical epithelium and induce the imbalance of the immune response. Other studies have shown that, in different parts of the world, the rate of cervical cancer combining with high-risk HPV infection is 86%-94%, and the infection of HPV 16,18 type is the most common. More and more evidence indicates that high risk HPV infection is closely related to the pathogenesis of cervical cancer and precancerous lesions. Immune system of the organism identifies and eliminates antigenicity foreign body to keep the physiological balance of the body, which is closely related to the occurrence and development of tumor. With the stimulation of the chronic inflammation, the body's immune regulation and cervical microenvironment change in the cervical cancer sufferers. How do the serises of changes happen? How does the body with inflammation and stimulation clear the virus infection? How do the tumor cells escape the monitor of the body's immune system in the process of formation? These problems have been attached more and more attention. In recent years, deeper study into the mechanism of cervical cancer reveals that the immune system of organism plays a vital role in the development of tumor.The occurrence and development of cervical cancer is closely related to the composition and quantity of local infiltrated lymphocytes. A large number of studies have shown that the prognosis of patient is related to the infiltration degree of lymphocyte in cervical cancer. Lymphocyte performs the leading role of the tumor immune function. Infiltration degree of lymphocyte in tumor tissue can be as a valuable indicator for the prognosis of cervical cancer. Tumor infiltrating lymphocyte (tumor infiltrating lymphocyte, TIL) is a kind of cell which has the function of invasion and antigen, which was found and separated in 1986 from a tumor-burdened mice by Rosenberg. TILs include T cells, B cells and NK cells, mostly T cells,which mainly express the phenotype of CD4~+and CD8~+. CD4~+ T lymphocytes can find tumor cells mainly by identifying the soluble antigen of those cells and activate a variety of immune cells, such as B cells, natural killer cells, macrophages, and cytotoxic T cells, which play the role of anti-tumor. At the same time, the CD4~+T cells can release a variety of cytokines to involve in the anti-tumor immunity. In addition to clearing target cells, CTL of CD8~+T cells (cytotoxic T cell) can identify and kill tumor cells and the cells infected by specific virus. Therefore, the number of CD8~+T cells determines the efficiency of killing target cells. CD4~+CD25~+T cell in TIL is regulatory T cell(regulatory T cell, Treg) with immunosuppressive effect.Foxp3 is one of the key transcription factors, which can affect the development and function of Treg cells. Foxp3~+T lymphocytes can reduce the expression of proinflammatory factor in gene transcription level and increase the expression of immunosuppressive factors so as to achieve the function of immunosuppression. In recent years, people pay a great deal of attention to the immunization of CD4~+, CD8~+ and Foxp3~+ T lymphocytes in tumor cells. Therefore, the study of the expression and significance of CD4, CD8 and Foxp3 in cervical cancer has a specific clinical significance in understanding the changes of the cervical local microenvironment and the diagnosis and treatment of cervical cancer.Materials and Methods1. Expermental samples75 cases of cervical tissue paraffin specimens were collected in the First Affiliated Hospital of Zhengzhou University from July 2012 to July 2014 and confirmed by biopsy.There are 63 cases of squamous cell carcinoma,aged 40 to 60 years, mean 50 years of age,excluding heart, liver and kidney disease. All patients have not done anti-tumor therapy nearly a month and have not used immunostimulants nearly 3 months. All patients staged with the International Federation Obstetrics and Gynecology(FIGO,2009)revised clinical staging,21 cases were stage ?,17 cases were stage ?,11 cases were stage ? and 14 cases were stage IV.2. Immunohistochemical stainingImmunohistochemical method was used to detect and the will of the prepared paraffin sections were dewaxed routinely hydration and archived wax blocks of 4 m thick serial sections. Using the conventional method of dewaxing to water and microwave antigen repair and SP Immunohistochemical method to check. To operate in accordance with the reagent instructions and an anti mouse monoclonal antibody of Foxp3 (1:100 concentration), rabbit monoclonal antibody against CD8 (concentration), rabbit monoclonal antibodies to CD4 (the concentration of 1:250), room temperature incubation fertility slices overnight, biotinylated rabbit/in universal IgG (1:200) room temperature incubation Yu Min; with DAB coloration hematoxylin stsining. Using PBS as a blank control, paraffin sections of endometrial carcinoma tissue were used as positive control.3. Statistical analysisExcel Windows was used to establish database, and the statistical analysis was performed by using SPSS 17.0. Two samples t test was used to compare the average number of two samples, the mean diversity compared with single factor analysis of variance; multiple sample rate compared with ?2 test. The difference with P< 0.05 was statistically significant for the different testing methods.Result1. Brown particles is positive staining.CD4 and CD8 are expressed in the membrane or cytoplasm of T cells, Foxp3 is mainly expressed in the nucleus, sometimes in the membrane. The expression of CD4 in cervical cancer (46%) is obviously lower than in normal cervical tissue(100%). The difference between groups is statistically significant,P<0.05.The expression of CD8 in cervical cancer (36.5%) is significantly lower than in normal cervical tissue(100%). The difference between groups is statistically significant, P<0.05.The expression of Foxp3 in cervical cancer (77.8%) is significantly higher than in normal cervical tissue(8.33%). The difference between groups is statistically significant, P<0.05.2. The Spearman correlation analysis shows that CD4 and CD8 expression has negtive correlation(r1=-0.470, r2=-0.538, P<0.05), and CD4 and CD8 has positive correlation (r=-0.538,P<0.05).3. The expression of CD4,CD8 and Foxp3 in cervical cancer has relationship with the stage grade and histological grade, but no relationship with the age,lesion size and HPV type. The expression of CD4 and CD8 in cervical cancer of advanced stage(stage ? and ?) is lower than that of early stage(stage ? and ?),while the expression of Foxp3 is higher. The difference between groups is statistically significant, P<0.05.The expression of CD4 and CD8 in cervical cancer of well differentiated cancer(G3) is higher than that of poorly differentiated cancer(G1?G2),while the expression of Foxp3 is lower. The difference between groups is statistically significant, P<0.05.Conclusion1. The reduction or lack of CD4~+ and CD8~+T cell in cervical microenvironment weakens the immunosuppression to tumor cells, which involves in the development of cervical cancer.2.The increase of Foxp3 T cell in cervical microenvironment strengthens the immunotolerance to tumor cells, which participatess in the development of cervical cancer. |
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