Value Of Serum Human Epididymis Secretory Protein4、CA125and ROMA(Risk Of Ovarian Malignancy Algorithm) In The Diagnosis Of Pelvic Mass

Pelvic mass occur in women of all ages, the clinical diagnosis and treatment is often a difficult clinical problem. In the United States, a woman has a5-10%lifetime risk of undergoing surgery for a suspected ovarian neoplasm, and within that group, an estimated13-21%chance of receiving a diagnosis of ovarian cancer. Although most pelvic masses are benign, the goal of the diagnostic evaluation is to exclude malignancy.Ovarian cancer is a common malignant tumor in female reproductive system, after the incidence of cervical cancer, endometrial cancer, ranked third, but the mortality rate is in the first place.In2012, it is estimated that22,300new diagnoses and15,500deaths from ovarian cancer will occur in the United States.Because of anatomic site hidden, lack of clinical symptoms and reliable screening, more than60%of women have advanced-stage disease (stage III-IV) at diagnosis. Therefore, ovarian cancer is known as a "silent killer". The5-year survival rate in women in whom Stage I ovarian cancer has been diagnosed exceeds90%; however, only20% of cancers are detected at this stage. The5-year survival rate is30-55%in women diagnosed at an advanced stage. There would have been notable improvements in mortality rates, because of satisfactory cytoreductive surgery and effective chemotherapy.A recent study indicate women who are operated on by surgeons who specialize in the management of ovarian cancer and at centers experienced in the management of patients with this disease have increased in overall survival. Unfortunately, fewer than half of ovarian cancer patients have their initial surgery by gynecologic oncologists who specialize in the management of ovarian cancer, that means many patients undergo inadequate surgical staging or receive suboptimal cytoreductive surgery at their initial surgery. How to use the existing medical resources, on the one hand, the patients with ovarian cancer can be transferred to the experienced cancer center to accept standard treatment, so as to improve the survival and quality of life; on the other hand, patients with benign ovarian diseases can be treated in grassroots medical institutions, so as to achieve the rational use of medical resources, reduce the burden of mental from patients. In recent years, seeking effective means to differentiate pelvic mass has become the focus of many scholars in different countries.Because of its noninvasive and objective, serum tumor marker detection has been widely used in clinical practice, and played an important role in screening, diagnosis, valuation of curative effect and recurrence monitoring.Carbohydrate antigen125(CA125), first discovered by Bast in1981, which is most widely used to predict the presence of malignancies in people with pelvic mass. It is recognized that CA125played an important role in diagnosis, valuation of curative effect and recurrence monitoring of ovarian cancer, especially for ovarian epithelial carcinoma. However, the sensitivity and specificity of CA125is not ideal.In recent years, human epididymis protein4(HE4) is considered to be one of the most potential ovarian cancer tumor markers. HE4was first identified in the distal epithelium of the epididymis by Kirchhoff in1991.Schummer et al. described for the first time in1999that HE4was overexpressed in epithelial ovarian cancer (EOC), but no expression or low expression in the benign disease and normal tissues (including ovarian tissue). Therefore, HE4was expected to be the ovarian cancer tumor marker. Since then, Drapkin et al. found that the different pathological tissue of epithelial ovarian cancer had different expression of HE4. In2008, Moore et al. examined a panel of biomarkers and found the dual marker combination of HE4and CA125produced the highest sensitivity of the various tumormarker combinations or any single tumor. A recent study indicates that the HE4measurement in healthy premenopausal women as well as in women with endometriosis can be carried out at any phase of the menstrual cycle, and irrespective of hormonal medication, extending the benefits of HE4use in clinical practice.In recent years, using tumor markers to construct mathematical model for pelvic mass discrimination attracts more and more attentions. In1990, Jacobs et al. proposed Risk of Malignancy Index for pelvic mass discrimination. RMI combined serum CA125level, ultrasound score and menopausal status, reduced the false positive rate of single factor diagnosis, improved specificity in preoperation diagnosis. Ultrasound diagnosis of physician experience have great influence on diagnosis, so different physicians will conclude differently for the same patient. It is bound to affect the objective evaluation of actual condition. The ROMA algorithm(Risk of Ovarian Malignancy Algorithm) was presented by Moore et al. in2009. The ROMA algorithm estimates the predictive index of malignancy by calculating the CA125and HE4values together with the menopausal status. Objective:To investigate the value of serum human epididymis secretory protein4(HE4), carbohydrate antigen125(CA125),and ROMA(Risk of Ovarian Malignancy Algorithm) in differential diagnosis of benign and malignant pelvic mass.Methods:Between May2013and September2013patients affected by pelvic mass, referred to the Department of Gynecology of Guangdong General Hospital were enrolled in the study. The level of HE4and CA125were measured by electrochemiluminescence immunoassay in the serum specimens of116women diagnosed the pelvic mass(39maligmant ovarian tumor,42benign ovarian tumor,35ovarian endometriosis) and36healthy women. The distribution characteristics of serum CA125, HE4in malignant ovarian tumor, benign ovarian tumor, ovarian endometriosis were analyzed. To investigate the relationship between serum CA125, HE4and malignant ovarian tumor histologic types and operation pathologic staging. When the benign ovarian masses group(ovarian benign tumor and ovarian endometriosis) was considered as control group, postoperative pathology results was the gold standard, HE4or CA125alone and combination assay were evaluated for sensitivity, specificity, positive likelihood ratio, negative likelihood ratio. The differential diagnosis value of HE4or CA125alone and combination assay were analyzed. According to Risk of Ovarian Malignancy Algorithm, the ROMA index of premenopause pelvic mass(n=80). and postmenopause pelvic mass(n=36) were calculated using ROMA software. Sensitivity, specificity, positive predictive value, and negative predictive value, accuracy were compared between premenopause group and postmenopause group.Results:1.The average age of ovarian malignant tumor group was52years old, which was significantly higher than that in benign ovarian tumor group (36years old) and ovarian endometriosis group (35years old). Postmenopausal patients accounted for a larger proportion (61.5%).2.The concentration of HE4was significantly higher in the malignant group when compared with all other groups(P<0.01), whereas no statistically significant differences were observed when comparing HE4in benign versus endometriosis (P=0.830), benign versus healthy (P=0.062), and endometriosis versus healthy groups(P=0.257).In contrast, the level of CA125was statistically elevated in malignant versus benign, malignant versus endometriosis, malignant versus healthy, endometriosis versus healthy, and endometriosis versus benign (P<0.01). The level of CA125was not statistically different only between the benign group and the group of healthy women (P=0.980).3.Serum CA125, HE4levels were significantly higher in ovarian malignant tumor group compared with the benign ovarian masses (ovarian benign tumor group and ovarian endometriosis group), differences were statistically significant (P<0.001).4.Ovarian malignant tumor group:The CA125levels was higher in postmenopausal women, the difference was statistically significant(P=0.007); The HE4levels was higher in postmenopausal women, the difference was statistically significant (P=0.006).Benign ovarian masses group:The CA125levels was higher in premenopausal group when compared with postmenopausal group, the difference was statistically significant (P=0.001); The HE4levels was higher in postmenopausal women, the difference was not statistically significant(P=0.053).5.Among the different tissue types of ovarian cancer, the median of serum HE4and CA125in serous ovarian cancer were the highest, and were higher than that in ovarian cancer with other tissue types (P<0.001).6.Median of serum HE4in late-stage ovarian cancer (stage â…¢-stage â…£) was higher than that of early-stage ovarian cancer (stageI-stageâ…¡)(P<0.001).7.When the benign ovarian masses group(ovarian benign tumor and ovarian- endometriosis) was considered as control group, ROC-AUC of CA125or HE4alone and CA125+HE4combined were0.823,0.848,0.894respectively. The diagnosis sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of HE4or CA125alone and addition assay were61.54%,85.71%,4.31,0.45;79.49%,87.01%,6.12,0.24and92.31%,74.03%,3.55,0.10respectively.8.In premenopausal patients with pelvic mass, cutoff value was set to11.4%, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the ROMA index were53.3%,89.2%,53.3%,89.2%,82.5%. In postmenopausal patients with pelvic mass, cutoff value was set to29.9%, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the ROMA index were87.5%,91.7%,95.5%,78.6%,88.9%. In addition, the study on ROMA and pathology of the anastomosis were compared, it was showed that:In premenopausal group, ROMA and postoperative pathological diagnosis consistent coefficient was0.426(Kappa=0.426), the consistent degree was statistically significant (P=0.000), but the agreement was general. In postmenopausal group, ROMA and postoperative pathological diagnosis consistent coefficient was0.760(Kappa=0.760), the consistent degree was statistically significant (P=0.000), and the agreement was good.Conclusion:1.HE4has the value on the diagnosis of ovarian cancer and has the advantages of high sensitivity and specificity compared with CA125.2.The serum level of HE4is associated with pathological types and operation stages of ovarian cancer. To a certain extent, it reflects the invasive ability of tumor, and is helpful for predicting the prognosis of patients.3.The Combination of serum CA125and HE4plays an important role in improving the sensitivity of diagnosis of ovarian cancer, reducing the misdiagnosing rate and providing an important reference for the differential diagnosis of pelvic mass.4.ROMA is a convenient tool, which can distinguish ovarian cancer from benign pelvic mass effectively. The predictive value of ROMA is significantly higher in postmenopausal patients compared with premenopausal patients.