Expression And Significance Of Pigment Epithelium-Derived Factor In Cervix Squamous Cell Carcinoma

BackgroudCervical cancer is the most common gynecologic malignant tumor whose incidence is high in our country. The number of new cases of cervical cancer patients every year in our country is about135000, which accounts for one third of the global. It influences women’s health and quality of life seriously. Cervical squamous cell carcinoma which is the most common pathological type of cervical cancer accounts for80%-85%of cervical cancer. Abnormal cell proliferation and angiogenesis are closely related to the happening of the cervical squamous cell carcinoma. Pigment epithelium-derived factor is first discoveryed by Tombran-tink in studying fetal retinal pigment epithelial cells in the growing of a nerve nutrients in1989. In the initial period of time PEDF is just be regarded as a kind of neurotrophic factor. With the development of research, we found PEDF protein in the human body also have the function of vascular inhibition and antitumor.ObjectiveTo investigate the expression of pigment epithelium-derived factor (PEDF) in early-stage cervical squamous cell carcinoma (ICC), cervical intraepithelial neoplasia (CIN) and normal cervical tissue samples (NCE). Analysis the relationship of PEDF with the proliferation index (PI), microvessel density (MVD), pelvic lymph node metastasis, vascular invasion, age, FIGO stage, tumor size, differentiation degree of clinicopathological parameters, preliminary investigate the role of pigment epithelium-derived factor in the occurrence and development of cervical squamous cell carcinoma. MethodsBetween February2010and June2011,30consecutive patients that underwent uterine surgery or cervical biopsy at the Department of Obstetrics and Gynecology of Shandong University Qilu hospital were enrolled in this study, including50cases in ICC,18cases in CIN,35cases in NCE. Immunohistochemistry were used to detect the expression of PEDF in ICC, CIN and NCE, as well as CD34and Ki-67. T-test was used to test MVD differences of three groups. φ correlation analysis was used to analyze the correlation of PEDF and MVD of ICC, as well as PEDF and Ki-67.χ2-test or fourfold table exact test was used to analysis the correlation between the expression of PEDF in ICC with clinicopathological parameters, as well as the difference among the three groups expression of PEDF, Ki-67.Results(1) By immunohistochemistry, we observed that PEDF protein was localized in the cytoplasm of NCE, CIN, ICC. And we also found that, squamous epithelium of NCE was strong positive mostly, PEDF in CIN downregulate, weakly positive; tumor tissue of ICC expression downward significantly, even part of the expression appears missing. PEDF-positive expression rate of NCE, CIN and ICC were100%,77.78%,48%, showing a significant downward trend. Merger weak positive and strong positive as positive, there was significant difference between positive and negative (P <0.05).(2) Mean MVD of NCE, CIN and ICC were11.74±2.35,23.12±5.74and38.44±6.79, showing a trend of increasing, among three groups, pairwise comparisons were significantly different (P<0.05).In the29cases of MVD-positive of ICC, the number of PEDF-positive and PEDF-negative cases was6and23respectively; In the21cases of MVD-negative of ICC, the number of PEDF-positive and PEDF-negative cases was18and3respectively. We can conclude that there is a negative correlation between the expression of PEDF and the value of MVD in ICC(P<0.01r=-0.6424).(3)Ki-67-positive expression rate of NCE, CIN and ICC were31.43%,83.338%and100%. Among the50cases of ICC, high expression of Ki-67was16and low expression was34, among the16cases, the number of PEDF-positive and-negative cases was3and13, among the34cases, the number of PEDF-positive and-negative cases was21and13. We can conclude that there is a negative correlation between the expression of PEDF and of Ki-67in ICC(P<0.01r=-0.4016).(4) There is a correlation between the expression of PEDF in cervical squamous cell carcinoma with pelvic lymph node metastasis and vascular invasion expression (P <0.05),And there is no correlation between the expression of PEDF in cervical squamous cell carcinoma and age, FIGO stage, tumor size and histological grade (P>0.05)Conclusion1.The expression level of PEDF is gradually reduced in the process of developing cervical carcinoma. The low expression of PEDF or loss in cervical carcinoma is an early event in tumor development.2.The expression of PEDF negatively correlated with Ki-67(P<0.01r=-0.4016) and CD34((P<0.01r=-0.6424)),PEDF possibly inhibit tumor proliferation by the promotion of apoptosis of tumor cells.3.PEDF protein was a gradual decrease or loss of expression in the development of in cervical squamous cell carcinoma, its expression was associated with lymph node metastasis and vascular invasion. The expression of PEDF which reduce or loss could strengthen invasion and metastasis of cervical squamous cell carcinoma. The PEDF protein expression level has the possibility to become judge cervical squamous cell carcinoma’s malignant degree and the patient’s prognosis.