| Objective1.Detecting the expression of B7-H4 protein in the tissue of different primary ovarian carcinoma.2.Focusing on investigation into the association between expression of B7-H4 protein and clinicopathological characteristics (age,clinical stage,tumor grade,ascites Cytology, lymph nodes metastasis)as well as follow-up in patients with serous cystadenocarcinoma, from which to infer the potential function of B7-H4 in the development and progression of serous ovarian cancer,as well.Materials and methods(1) Cases collection:'All tissue samples,64 cases in total,which were collected from patients with primal epithelial ovarian tumor who receive initial diagnosis and surgical therapy in gynecological department of Jinan Military General Hospital during certain time from May of 2003 to October of 2009, were categorized as a study group,all of which including 47 patients with parimy malignant epithelial ovarian tumor,5 patients with borderline epithelial ovarian tumor,8 patients with benign epithelial ovarian tumor. Besides,we selected 6 normal ovarian tissues as control group,which were cut off, in corresponding time to the control group,from patients with "hysteromyoma" or other benign diseases.(2) Experimental method:In our study we used s-p immunochemical method to detect the status of the B7-H4 protein expression in epithelial ovarian tumor.(3) Follow-up:All of patients with serous ovarian cancer were underwent follow-up,to record the patients clinical data precisely including the results of clinical examination,the therapeutic method,the state of survival and so on,then to carry out survival analysis under the association with the state of B7-H4 protein expressed in ovarian cancer tissues.(4) Statistical analysis:The SPSS 16.0 software were used for statistical analysis in testing this experimental data. Aχ2 test,Fisher's Exact test, Wilcoxon Rank Sum test and Kruskal-Wallis test were used to examine the significant separation of B7-H4 protein expression between different histological types, clinical stage, tumor grade,age, lymphatic metastasis and other clinicopathological characteristics.In multiple comparison test among several samples,we utilized partitions of x2 method.In nonparametric tests, the twin-to-twin comparison among multiple independent samples use Nemenyi test.In analyzing the correlation between B7-H4 protein expression and clinicopathological characteristics in patients with ovarian cancer we used Spearman correlation test. In the univariate analysis, Kaplan-Meier product-limit survival analyses and life table survival analyses were performed, and the log rank test was utilized to examine the significance of the differences of survival distributions between groups. In multivariate analysis,Cox proportional hazards regression models were developed. The cut-point was determined as the 95th percentile,when P-values<0.05 were considered to be statistically significant.Results1. B7-H4 protein stained in buffy color mainly located in the cytoplasm and cell surface of epithelial tissue components, which stained diffusely and in graininess showing when were observed in ovarian cancer,but in some kind of sparseness and weak point when expressed in benign and normal ovarian tissues.2. B7-H4 protein expression was detected in 1/6 normal ovarian tissues, in 2/8 ovarian benign epithelial tumor,inl/5 ovarian borderline epithelial tumor, in 40/51 ovarian malignant epithelial tumor, respectively.The differences of B7-H4 protein expression between ovarian cancer and control group were statistically significant, (χ2=10.14,P<0.008);The differences of B7-H4 protein expression between ovarian cancer and non-malignant ovarian tumor were statistically significant,(x2=10.14,P<0.008).The differentces between other groups were not statistically significant, wholly, (P>0.008).3. B7-H4 protein expression was detected in 31/33 serous ovarian cancer,in 4/5 endometrioid ovarian cancer,in 4/4 clear cell ovarian cancer,in 1/9 mucinous ovarian cancer, respectively, the B7-H4 protein expression were different among these 4 different histological types, and the differences among them were statistically significant,(x2=20.446,P<0.05).The B7-H4 protein expression were different between mucinous ovarian cancer and non-mucinous ovarian cancer, the differences between any other of them were statistically significant,as well,(P<0.05).But in each of them among non-mucinous ovarian cancer, the differences of B7-H4 protein expression were not statistically significant,(x2=1.460,P>0.05).4. In serous ovarian tumor tissue,the B7-H4 protein expression in malignant tumor were obviously high than in any other of group between borderline tumor and benign tumor, the differences of B7-H4 protein expression among them were statistically significant, (χ2=12.698, P<0.05).5.The correlation between B7-H4 protein expression in serous ovarian cancer and characteristics the patients have taken.The rate of B7-H4 protein expression in cancer tissues with good different-iation or moderate differentiation and poor differentiation was 83.3%,94.1%, 100%,respectively, the B7-H4 protein expression in cancer tissue with poor differentiation was more good than that of in cancer tissues with good differentiation or moderate differentiation,the separation among them was statistically significant, (χ2=12.531,P<0.05). Following the grade of the tissue differentiation descending,the positive rate and the intensity of B7-H4 protein expression in ovarian cancer tissues would increase,in which there were obviously positive correlation between them,(rs=0.626,P<0.05). The positive rate of B7-H4 protein expression in ovarian cancer tissues which have taken placed lymphatic metastasis was 100%(10/10),that was prominent high than in the tissues with negative lymphatic metastasis (12/14,positive rate85.7%),the differences between of which were statistically significant,(Z=-3.813,P<0.05). There were also obviously positive correlation between them, (rs=0.801,P<0.05).All the differences of B7-H4 protein expression among groups with different clinical stage or different age and different ascites-cytology were not statistically significant,(P>0.05).6. The hazard factors which could exert some extent of impact on the follow-up of the patients with serous ovarian cancer.The Hazard Ratio (HR) from univariate analysis of B7-H4 and other 5 fact-ors (FIGO stage,tumor grade,age, residual size,sum of chemotherapy courses) was significant.However, the prognostic value of B7-H4 and the sum of chemo-therapy courses were attenuated and rendered insignificant when all of the factors in above were included in the multivariate analysis(P>0.05,totally).Conclusions1.The expression of B7-H4 protein in serous ovarian cancer, endometrioid ovarian cancer and clear cell ovarian cancer was high, however,in mucinous ovarian cancer and benign ovarian tumor were weak or negative,from which we could infer B7-H4 may take a role in the development of serous ovarian cancer endometrioid ovarian cancer and clear cell ovarian cancer and may be a new tumor marker with potential diagnostic value for ovarian cancer especially for serous ovarian cancer,to provide patients with a new target for biotherapy as well.2.The levels of B7-H4 protein expression increased with tumor grade and lymphatic metastasis.There were a significant positive correlation conveyed in our study between them, all of which indicated that B7-H4 protein expression may play a role in promoting malignant transformation of epithelial cells and the expansion of tumor.3.Though there were no relationship between the B7-H4 protein expression and the patient's follow-up detected in our test, respecting the significant relationship to patient's clinicopathological characteristics,we can infer that the B7-H4 protein expression may be a potential hazard factor on follow-up.
|
PDF Full Text Request