Value Of Serum Human Epididymis Secretory Protein 4, CA125 And ROMA (Risk Of Ovarian Malignancy Algorithm) In The Differential Diagnosis Of Pelvic Mass

Objective to evaluate the value of serum human epididymal secretory protein 4 (HE4), carbohydrate antigen 125 (CA125) and the risk of ovarian malignancy algorithm (ROMA) in differential diagnosis of benign and malignent pelvic mass.Methods The level of HE4 and CA125 were measured by enzyme-linked immunosorbent assay (ELISA) in the serum specimens of 124 women diagnosed with pelvic mass(38 maligmant ovarian mass,86 benign pelvic mass) and 40 healthy postmenopausal women, Using the serum CA125 and HE4 values, a predictive index (PI) and predicted probability(PP) were calculated for each patient by the separate logistic regression algorithm based on their menopausal status.The cut-off point of HE4 were determined by receiver operating characteristic curves (ROC curve), For CA125, the normal upper limit was 35ku/L, according to reagent box proposal.Statistical analysis was performed with SPSS statistical software(v13.0).The K-S inspection method was applied for the test of normality, all the measurement data were skewed distribution, the HE4 and CA125 levels were expressed with a median (M).Using two independent samples nonparametric tests (Mann-Whitney Test) to compare the level between groups, the differences between two indexes within the same group were calculated by four tables. The differential diagnostic accuracy of each marker,the combination of the two markers and ROMA of benign and malignant pelvic mass were assessed by of ROC-AUC.Results (1)The average age of ovarian malignant tumor group was significantly higher than that of benign pelvic mass group (P< 0.01), the difference was statistically significant.(2) The cut-off point of HE4 of premenopausal was 53.53pmol/L (Se 80%, Sp73.33%), postmenopausal 53.53pmol/L (Se 88.89%, Sp100.00%).If not consider the menstrual state, HE4 cut-off poin is 107.8pmol/L. (3) Ovarian malignant tumor group: premenopausal HE4 and CA125 levels below two levels after menopause, but the differences between the two groups were not statistically significant. (HE4 P= 0.133, CA125 P= 0.113).Benign pelvic mass group:before and after menopause, HE4 levels of two groups were similar, the difference was not statistically significant (P= 0.539). CA125 levels in premenopausal group were higher than that of postmenopausal group, the difference was statistically significant (P= 0.037)..(4)ROMA classified patients at a low or high risk for malignant disease. in the premenopausal group, there were 12 cases classified as high-risk group,8 cases classified as low risk group.In the postmenopausal group, all 18 patients were classified as high risk.The two groups together, in 38 patients with ovarian malignant tumors,30 cases were classified as high risk,8 cases classified as low risk.Benign pelvic mass in a patient, in the premenopausal group,16 cases classified as high-risk groups (including 10 cases of ovarian endometriosis patients),44 cases classified as low risk group.In the postmenopausal group, there were 4 cases classified as high-risk group,22 cases classified as low risk group. Within the group of total benign pelvic mass included 86 cases,20 cases were classified as high risk,66 cases classified as low risk.(5) In the premenopausal cohort::HE4+CA125 combined detection had the highest sensitivity, 90%; HE4 alone had the highest specificity,96.7%.The positive predictive value of HE4 alone was higher than the other three groups.The differences of negative predictive value among 4 kinds of methods is not significant. The ROC-AUC of HE4, CA125, HE4+CA125 and ROMA were 0.775,0.733,0.853,0.777.There were no significant difference among them.In the postmenopausal cohort:The sensitivity and negative predictive value of CA125 alone, HE4+CA125 and ROMA were 100%.The specificity and positive predictive value of HE4 was 100%. The ROC-AUC of HE4, CA125, HE4+CA125 and ROMA were 0.974,0.991,0.991, there were no significant difference among them.Do not consider the menopause:The specificity and the positive predictive valueof HE4alone were higher than those of CA125 single detection and combined detections. CA125 alone had a equal sensitivity to HE4+CA125 combined, and were higher than that of HE4 alone. ROC-AUC of HE4 or CA125 alone and HE4+CA125 combined is 0.859,0.862,0.920 respectively. ROC-AUC of two individual testing had no significant difference (P= 0.967), the differences among two individual detection with combine detection were statistically significant (P< 0.05).Conclusion:(1) HE4 has the value on the diagnosis of ovarian malignant and has the advantages of high specificity compared with CA125.But as a single marker its value in the differential diagnosis of pelvic mass is not better than that of CA125 single detection.(2) Combined HE4 and CA125 is a more accurate means in differential diagnosis of pelvic mass compared with HE4 or CA125 single applied.(3) The dual marker algorithm utilizing HE4 and CA125 to calculate a ROMA value does not show better performance than HE4 and CA125 alone in this study.