| Ovarian epithelial cancer (EOC) is the highest mortality gynecologic malignancies. Although improved surgical techniques, clinical application of cisplatin, taxol and other chemotherapy drugs, bring many of life to patients, the 5-year survival in patients with ovarian cancer still has no significant increase. Because early-stage ovarian cancer is generally asymptomatic, and the lack of effective screening method, about 80% of the patients at diagnosis have advanced stage disease. The value of CA125 in ovarian cancer diagnosis, monitoring the process, efficacy and recurrence has been confirmed, but CA125 is limited by poor sensitivity and poor specificity for screening ovarian cancer. Therefore, searching for ovarian cancer markers with higher sensitivity and specificity and effective treatment is extremely important in clinical work. B7-H4 is a recently identified B7 family member, which is known to be a T cell costimulatory molecule down-regulated in the T cell-mediated immune response and related with tumor immue escape. Forkhead/winged-helix transcription factor (Foxp3) is a newly discovered specific marker to determine regulatory T cells. Foxp3~+Treg plays an important role in immune suppression and promotes immune escape of tummor cells. Studies have shown that B7-H4 protein and Foxp3~+Treg are overexpressed in variety tumors, they may become new tumor markers. In addition, B7-H4 and Foxp3~+Treg suppress tumor immunity, so they are expected to become new target for tumor immunotherapy. However, the role of B7-H4 and Foxp3~+Treg on the prognosis and the immunotherapy of ovarian cancer need to be further studied. This study was designed to evaluate the expression of B7-H4 protein and Foxp3~+Treg in ovarian epithelial tumors, analys the relationship between B7-H4 and Foxp3~+Treg, explore the expression of B7-H4 and Foxp3~+Treg effect on the process and the prognosis of ovarian cancer patients with clinical data. To provide a new basis for diagnosis and immunotherapy of ovarian cancer.Methods1. A total of 63 paraffin-embedded epithelial ovarian cancer tissue blocks were obtained from the Department of Gynecologic Oncology at the Cancer Affiliated Hospital of Shantou University Medical College in the period between October 1998 and March 2009, and clinical data of these patients was collected. 10 tumors of low malignant potential , 16 cases of benign ovarian tumors were added in either. Control group included 10 normal ovary tissues.2. The immunohistochemical detection system was used to detect the expression of B7-H4 protein and Foxp3~+Treg in epithelial ovarian tumors.3. The staining intensity of B7-H4 protein was quantified with the aid of Image Pro Plus (IPP) 6.0 Software.4. SPSS Statistics 17.0 software was used to analyze the relationship between the expression of B7-H4 protein and Foxp3~+Treg in EOC,and their connection with pathological classification, clinical stage, histological grade, distant metastasis and clinical prognosis.Results1. The positive rate of B7-H4 protein and Foxp3~+Treg in EOC were 54.0% and 66.7%, and both of them were negative in borderline ovarian tumors, benign ovarian tumors and normal ovarians, the difference was statistically significant (P <0.001).2. The intensity of B7-H4 protein is positively correlated with the number of Foxp3~+Treg in EOC, P=0.01,r=0.324.3. The relationship between B7-H4 protein expression and the clinicopathological significance of EOC: The intencity of B7-H4 protein expression in advanced epithelial ovarian cancer (â…¢-â…£stage) ( density mean=0.0320), was significantly higher than that in early ovarian cancer (â… -â…¡stage) (density mean=0.0109), P = 0.028. B7-H4 protein expression of ovarian cancer whose capsule ruptured (density mean=0.0315), was significantly higher than that in the complete ones (density mean=0.0078), P = 0.016. The positive rate of B7-H4 protein in EOC was not related with tumor histological type, tumor grade and tumor location (P> 0.05).4. The relationship between Foxp3~+Treg expression and the clinicopathological significance of EOC: The positive rate of Foxp3~+Treg expression in the majority of ovarian epithelial carcinoma (37/44, 84.1%) was much higher than in other types of epithelial ovarian cancer (5/19, 26.3%), the difference was statistically significant (P <0.0001). The positive rate of Foxp3~+Treg in EOC was not related with tumor grade, clinical stage, tumor capsule integrity, tumor location and omentum/lymph node metastasis (P> 0.05). However, the levels of Foxp3~+Treg expression related with tumor histological type, clinical stage, tumor location and omentum metastasis (P <0.05). 5. Using Kaplan-meier analysis prognostic factors of 63 epithelial ovarian cancer patients. Results showed that clinical stage (P = 0.030), tumor location (P = 0.025), cytoreductive surgery residual tumor size (P = 0.002) and Foxp3~+Treg (P = 0.012) that may affect ovarian cancer prognosis. Using multivariate Cox regression analysis on 63 patients with epithelial ovarian cancer survival time. The results showed that, B7-H4 protein expression, Foxp3~+Treghight, advanced stage, grade three, cytoreductive surgery residual tumor>1cm were poor prognostic factors in EOC patients (P <0.05).Conclusions1. B7-H4 and Foxp3~+Treg are expected as tumor marker for diagnosis of EOC.2. The intensity of B7-H4 protein is positively correlated with the number of Foxp3~+Treg in EOC. Suggest they may have a synergistic effect in the inhibition of tumor immunity.3. The intensity of B7-H4 protein and the levels of Foxp3~+Treg expression wre related to clinical stage of EOC. Suggest B7-H4 and Foxp3~+Treg may affect the progression of EOC.4. B7-H4 and Foxp3~+Treg expression were the impact of ovarian cancer prognosis, they could be used as indicators of prognosis for EOC, and provide a new way for targeted therapy. |
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