Expression Of Hla Class I, CD8 And CD4 And Their Clinical Significances In Various Cervical Diseases

Objective: Cervical cancer is the second leading cause of cancer related death among women worldwide. In spite of early screening,new cases and deaths are still at a high level each year. Especially in economically underdeveloped areas, women were often in the advanced stage and five-year survival rate decreased once they were diagnosed with cervical cancer. It has been acknowledged that the systemic and local immune status play important roles in clearance of tumor cells. The mechanism of escape from immune-surveillance is responsible for the growth of malignant tumor, one of which is down-regulating the expression of human leukocyte antigen classâ… ( HLA-I), inducing the decrease of CD8+ T lymphocytes for activation, then reducing the killing effect for tumor cells and leading to the progression and metastasis. In this research, we examined the expression of HLA-I, CD8 and CD4 in cervical cancer, cervical intraepithelial neoplasia(CIN), chronic cervicitis and peri-cancer tissues using SP immunohistochemistry, to understand local immune state of cervix and investigate their association with cervical cancer. Methods: The SP immunohistochemistry was used to detect the expression of HLA-I, CD8 and CD4 in patients with cervical cancer, cervical intraepithelial neoplasia(CIN), chronic cervicitis and peri-cancer tissues, who were diagnosed by clinical pathology. Each of these four tissues was chosen 20 cases, sliced and HLA-I, CD8, CD4 monoclonal antibodies were applied to them according to the steps of immunohistochemical kit (Maixin Bio. Fuzhou), then staining by DAB. PBS instead of primary antibody was used as blank control and tonsillar tissue as positive control.Results: Flaxen to brown particles on cell membranes or in cytoplasm were recognized as staining positive cells and comprehensive assessment was given according to the ImmunoReactive Score that evaluated the proportion of the cells expressing such molecules and the intensity of the staining. The percentage of positive tissue staining of HLA class I antigen in cervical cancer, CIN, chronic cervicitis and peri-cancer tissues were 40%, 95%, 100.0% and 100.0%, respectively. And the percentage of CD8 in various tissues was 35%, 95%, 100% and 100.0%, respectively. The positive tissue staining percentage of CD4 in the tissues above was 45%, 80%, 100% and 100%, respectively. The percentage of positive tissue staining of HLA-I, CD8 and CD4 were signifi cantly lower in tissues of cervical cancer when compared with other tissues (P < 0.01). No correlation between positive tissue staining of HLA-I, CD8, and CD4 and clinicopathologic profiles was observed (P > 0.05). A positive correlation was found between HLA-I and CD8 expression (Spearman's correlation r =0.913,P<0.001).Conclusion: The expression of HLA-I, CD8 and CD4 are down-regulated or deleted in CIN and cervical cancer, which suggest the local immune status of cervix is closely related to the development and progression of CIN and cervical cancer.