The Value Of Serum HE4 In Epithelial Ovarian Cancer Diagnosis And Monitoring

Objective: Epithelial ovarian cancer (referred to as ovarian cancer) is a malignant tumor, which seriously threaten the women health. Although incidence rate of ovarian cancer after the Cervical and Palace cancer, the mortality rate ranks first in the female reproductive system. Early symptoms of ovarian cancer are not obvious, 70% to 80% of patients who see doctor is too late, five-year survival rate of patients with advanced ovarian cancer only 20% to 30%. However, five-year survival rate of early ovarian cancer up to 90% by the effective treatment. Therefore, improving the early diagnosis of ovarian cancer can increase the prognosis of ovarian cancer. In this study, enzyme-linked immunosorbent assay (ELISA) double antibody sandwich assay in patients with ovarian cancer, epithelial benign ovarian tumor patients and female healthy volunteers' serum HE4, CA125 expression levels, at the same time analysis ovarian cancer patients' serum HE4 according to different clinical stages and different pathological types and grades. Ovarian cancer patients with the cytoreductive surgery, we analysized the serum levels of HE4 expression which includes before and after surgery, and compared with the homologous serum CAl25 levels. Exploring the value of HE4 with CAl25 as a tumor marker for ovarian cancer early diagnosis, monitoring evaluation . Methods:We selected January 2008 to July 2010 Bethune International Peace Hospital, Obstetrics and Gynecology untreated ovarian cancer patients and patients with epithelial benign ovarian tumor. All patients were diagnosed by postoperative pathology, of 44 cases were ovarian cancer, 56 cases were epithelial benign ovarian tumor, 40 cases were female healthy volunteers. Sterile extraction patients, healthy volunteers fasting blood 3 ~ 4ml, placed in vacuum blood coagulant. Put it aside for about 1 hour to be fully solidified to 4℃, 3000r/min, centrifugal 15min, supernatant was drawn into sterile EP tube, and stored at -20℃refrigerator under test.1 Cornell by the Swedish grid (ConAg) HE4 kit produced by enzyme-linked immunosorbent assay (Enzyme. 1inked Immunosorbent Assay, ELISA) double antibody sandwich assay the content of the serum HE4.2 The serum CA125 concentration in the Bethune International Peace Hospital, Centre for Reproductive Genetics routine by chemiluminescence measured.3 The female healthy volunteers and epithelial benign ovarian tumor r groups as a reference population, the cut-off point was obtained ROC curve, calculated serum HE4 in the diagnosis of ovarian cancer in the sensitivity and specificity. Comparison of the value of serum HE4 alone and HE4 with CAl25 as cancer marker in diagnosis of ovarian cancer.4 Statistical methods: statistical results to the (median,IQR), application of statistical analysis software was SPSS13.0, compared measurement data between groups, count data between groups and the diagnostic performance evaluation analysis. Sided P<0.05 considered significant difference.Results:1 Compared with Ovarian cancer, epithelial benign ovarian tumor group and healthy female volunteers: densities of three groups were (373.3 pM, 137.3 -771.1 pM), (43.2 pM, 34.0-52.1 pM), (50.4 pM, 46.4-52.3 pM), HE4 was used to compare the level of diversity of the rank sum test, KW test method (Kruskal-Wallis H Test),χ2= 64.5, P<0.001, the difference was statistically significant. The level of peripheral serum HE4 in Ovarian cancer patients was significantly higher than epithelial benign ovarian tumor, Wilcoxon rank sum test statistic (z =- 7.15, P<0.001) and healthy volunteers group (z =- 6.09, P <0.001), the difference was statistically significant.2 Different pathological types of ovarian cancer patients the serum levels of HE4 comparison: serous carcinoma (643.0 pM, 346.2-1077.3 pM), mucinous carcinoma (158.6 pM ,51.3-232.5 pM), endometrioid carcinoma(772.3 pM, 608.2-934.9 pM), clear cell carcinoma(- -) of which serous carcinoma group was significantly higher than in peripheral blood HE4 mucinous carcinoma group (Wilcoxon rank sum test statistic (z =- 3.43, P =0.001<0.05) difference was statistically significant. The sample size of patients with endometrial cancer and clear cell carcinoma respectively is of 4 cases and 2 cases, which too small to conduct comparisons.3 Comparison of different differentiation of serum HE4 evels in Ovarian cancer group: Gl-class group of rank differentiation (well differentiated) (58.7 pM,31.3-210.3 pM), G2-level group (differentiated) (529.3 pM, 115.1-812.0 pM), G3-level group (poorly differentiated) (609.2 pM, 232.5-1080.9pM), HE4 serum levels of the three test methods by KW,χ2= 13.4, P = 0.001<0.05, significant difference, the lower differentiation, the higher serum HE4.4 Comparison of different surgical - pathologic staging serum HE4 levels of Ovarian cancer patients: the clinical basis of surgical staging of ovarian cancer staging FIGO2000. Ovarian cancer stageⅢ-Ⅳ(165.2 pM, 45.0-483.1 pM) HE4 serum levels were significantly higher than that of stageⅠ-Ⅱ(626.6 pM, 231.7-1078.3 pM) group (Wilcoxon rank sum test z = - 2.93, P = 0.003<0.05), the difference was statistically significant.5 Compared with serum HE4 of Ovarian cancer group which preoperative and postoperative(after 1 week): of 44 cases, 22 underwent cytoreductive surgery, 1 week after surgery(194.8 pM, 36.3-500.2 pM), the serum HE4 lower compared with preoperative(372.6 pM, 124.2-812.5 pM). Using Wilcoxon signed-rank test statisticsvolume (z =- 3.98, P < 0.001), the difference was statistically significant.6 Different pathological types of epithelial benign ovarian tumor HE4 serum levels were varied between Serous cystadenoma(39.9pM, 33.5-49.4 pM) and mucinous cystadenoma(47.8 pM, 37.7-56.8 pM), Wilcoxon rank sum test statisticsvolume (z=-1.54, P=0.12>0.05), the difference was not statistically significant.7 HE4 serum levels on diagnosis of ovarian cancer: statistical software application SPSS13.0 ROC curve analysis revealed a high degree of diagnostic accuracy of HE4. (In the pathological diagnosis was the gold standard for the diagnosis, 44 cases of ovarian cancer patients as case group and control group for the remaining 56 cases of epithelial benign ovarian tumor and 40 cases of healthy volunteers,96 patients total) ROC area under the curve (area under the ROCcurve, AUC) was 0.91, standard error 0.04, approximately 95% of its reference interval of confidence (0.83-0.98).8 detect serum HE4 as a biomarker to distinguish ovarian cancer,epithelial benign ovarian tumor and female healthy volunteers. we made cut-off= 73.09pM. Serum HE4 in ovarian cancer diagnostic criteria are as follows: When the concentration of serum HE4≥73.09 pM when the diagnosis is positive; when the concentration of serum HE4<73.09 pM when the diagnosis was negative. At this point sensitivity (sensitivity) = 86.4%, specificity (specificity) = l.9 Serum HE4 and CA125 for ovarian cancer diagnosis of patients (in pathological diagnosis as the gold standard for diagnosis, 44 ovarian cancer patients as case group, 56 cases of epithelial benign ovarian tumor as the control group. serum CA125≥35.0 u / ml diagnosed as positive; <35.0 u / ml diagnosed as negative). When the concentration of serum HE4≥73.09 pM when the diagnosis is positive ; when the concentration of serum HE4<73.09 pM when the diagnosis was negative.HE4 of the ROC curve AUC = 0.92, standard error of 0.04, CA125 the ROC curve AUC = 0.98, standard error 0.01.HE4 and CA125 diagnostic precision rate was 95.7%, 90.0% are high.Serum HE4 test specificity is 1, the positive predictive value of 1, Youden index was 0.86 higher than those of CA125, the sensitivity of detection was 86.4%, 94.1% negative predictive value was slightly lower than the CA125.10 Combined serum HE4 and CA125 to diagnostic performance analysis, the joint sensitivity was 95.5% and combined specificity was 89.6%, combined precision rate was 91.4%. Compared with CA125 alone or serum HE4, the diagnostic sensitivity was increased. Conclusion:1 Application of double-antibody sandwich ELISA method in patients with ovarian cancer were significantly higher than that of HE4 in patients with epithelial benign ovarian tumor and female healthy volunteers, and HE4 levels of patients with ovarian cancer were associated with clinical pathology, staging and differentiation degree.2 Serum HE4 was sensitivity and specificity in diagnostic ovarian cancer, which in the identification and diagnosis of epithelial benign ovarian tumor and ovarian cancer specificity than CA125, clinical performance is better. Expected to become a new serum tumor markers of ovarian cancer in clinical testing and further improve the early diagnosis of ovarian cancer.3 Manager to cytoreductive surgery for ovarian cancer patients after surgery compared with preoperative serum HE4 significantly reduced. Therefore, serum HE4 can be used to an effective indicator to monitor the ovarian cancer therapeutic effect.