Clinical Usefulness of Cancer Antigen (CA) 125, Human Epididymis 4, and CA72-4 Levels and Risk of Ovarian Malignancy Algorithm Values for Diagnosing Ovarian Tumors in Korean Patients With and Without Endometriosis

BACKGROUND: Tumor markers are useful for detection and preoperative evaluation of ovarian tumors. We evaluated the clinical usefulness of cancer antigen (CA) 125, human epididymis 4 (HE4), and CA72-4 levels and Risk of Ovarian Malignancy Algorithm (ROMA) values for differential diagnosis of malignant and borderline tumors among suspected ovarian tumors, and the effects of endometriosis on these tumor markers. METHODS: In a total of 266 patients (213, 14, and 39 with benign, borderline and malignant tumors, respectively), CA125, HE4, and CA72-4 levels were measured, and ROMA values were calculated. Medians of each marker were compared among the three groups. The area under the ROC curve (AUC), sensitivity, and specificity were calculated to analyze the diagnostic performance of each marker. RESULTS: All markers were significantly higher in the malignant group than in the benign group. HE4 levels and ROMA values were significantly higher in the malignant group than in the borderline group. ROMA value had the highest AUC for distinguishing the malignant and borderline groups from the benign group in premenopausal (0.773) and postmenopausal (0.927) patients. CA125 level was significantly higher in patients with endometriosis than in those without (P<0.001), whereas HE4 and CA72-4 levels were not affected by endometriosis (P=0.128 and 0.271, respectively). CONCLUSIONS: ROMA value is the best marker to distinguish malignant and borderline tumors from benign tumors in pre- and postmenopausal patients. HE4 and CA72-4 levels provide information on possible CA125 elevation due to endometriosis.

Comparison of serum cancer antigen 125, human epididymis protein 4, ROMA, and CPH-I for diagnosis of ovarian cancer in Chinese patients with ovarian mass / 南方医科大学学报

OBJECTIVE@#To compare the performance of serum cancer antigen 125 (CA125), human epididymis protein 4 (HE4), Risk of Ovarian Malignancy Algorithm (ROMA) and Copenhagen index (CPH-I) for differential diagnosis of benign and malignant diseases in patients with ovarian mass.@*METHODS@#We retrospectively analyzed the data of 719 women with pelvic mass, and the performance of preoperative serum levels of CA125 and HE4, ROMA and CPH-I for differential diagnosis of the masses was compared.@*RESULTS@#Of the 710 women analyzed, 531 were diagnosed with benign ovarian lesions, 44 with borderline ovarian tumors (BOTs), 119 with epithelial ovarian cancers (EOCs), and 25 with non-EOCs. In differentiating ovarian cancer (OC) and BOT from benign lesions, the area under the receiver-operator characteristic (ROC) curve (AUC) was 0.854 for HE4, 0.856 for ROMA, 0.854 for CPH-I, and 0.792 for CA125, demonstrating better diagnostic performance of HE4, ROMA, and CPH-I than CA125 alone; the diagnostic sensitivity was 56.9% for HE4, 70.2% for CA125, 69.1% for ROMA, and 63.8% for CPH-I; the specificity was the best with HE4 (94.4%) and CPH-I (94.7%). In sub-analysis of EOC benign lesions, the AUCs of HE4, ROMA, and CPH-I increased to 0.946, 0.947, and 0.943, respectively, all greater than that of CA125 (0.888). In other sub-analyses, HE4, ROMA, and CPH-I all showed greater AUCs than CA125 alone.@*CONCLUSIONS@#This study confirms the accuracy of HE4, ROMA, and CPH-I for differentiating malignant from benign ovarian mass, and all these 3 tests show better performance than CA125. Furthermore, HE4 and CPH-I is superior to ROMA and CA125 in terms of specificity, while CA125 and ROMA have better diagnostic sensitivities.

Diagnostic value of serum human epididymis protein 4 and carbohydrate antigen 125 combined with risk of ovarian malignancy algorithm index for ovarian cancer / 肿瘤研究与临床

Objective To investigate the clinical value of serum human epididymis protein 4 (HE4), carbohydrate antigen 125 (CA125) combined with risk of ovarian malignancy algorithm (ROMA) index in the diagnosis of ovarian cancer. Methods A total of 541 patients in the Department of Gynaecology in Baoji Central Hospital from August 2016 to February 2018 were collected. The serum HE4 and CA125 levels were measured by using electrochemiluminescence immunoassay in 226 cases of ovarian cancer (ovarian cancer group), 315 cases of ovarian benign disease (ovarian benign disease group) and 100 female healthy people (the control group). ROMA index was calculated according to ROMA model and the results were analyzed statistically. Results The levels of serum HE4, CA125 and ROMA index were significantly different in premenopausal and postmenopausal ovarian cancer group, ovarian benign disease group and the control group (all P<0.05). The sensitivity and Yonden's index of the three combined diagnosis of serum HE4, CA125 and ROMA for premenopausal ovarian cancer were 97.01 ％ and 77.01 ％ respectively, which were higher than those of a single detection (HE4:79.37％, 69.11％;CA125:76.06％, 66.38％;ROMA index:89.55％, 72.41％;χ2sensitivity=12.35, P=0.000;χ2Yonden's index=6.460, P=0.013. The sensitivity and Yonden's index ofthe three combined diagnosis of serum HE4, CA125 and ROMA for postmenopausal ovarian cancer were 98.99 ％ and 82.99 ％ respectively, which were higher than those of a single detection (HE4: 86.90 ％, 79.40 ％; CA125: 82.98 ％, 76.31 ％; ROMA index: 93.54 ％, 80.64 ％; χ2sensitivity = 14.25, P = 0.000;χ2Yonden's index= 4.822, P= 0.031). The area under the curve of the combined detection of three indicators was higher than that of a single detection (premenopausal group: 0.871 vs. 0.682, 0.626, 0.708; postmenopausal group: 0.981 vs. 0.724, 0.705, 0.833), and there were significant differences (premenopausal group: χ2 =11.24, P= 0.000; postmenopausal group: χ2= 16.38, P= 0.000). Conclusion The combined detection of serum HE4, CA125 and ROMA index can increase the sensitivity and accuracy for diagnosing ovarian cancer, which can provide a more reliable basis for diagnosis and screening of ovarian cancer.

The value of HE4, CA125, and ROMA model in diagnosis of the ovarian carcinoma / 重庆医学

Objective To explore the value of human epididymis protein 4(HE4),cancer antigen 125(CA125) and the risk of ovarian malignancy algorithm(ROMA) in the diagnosis of ovarian cancer.Methods Electrochemical luminescence and Enzymelinked immunosorbent assay (ELISA) were used to determine the levels of serum HE4,CA125 in 56 patients with ovarian carcinoma,73 cases of ovarian benign tumor and 50 health women,and the ROMA was calculated by HE4 and CA125 levels depending on the menopause state,drawing the receiver operating characteristics(ROC) curve and calculating the area under the curve(AUC).Results The average levels of the HE4,CA125 and the value of the ROMA were (345.33±605.03)pmol/L,(701.46±1 500.30) U/mL,(58.72±31.00) ％ in the ovarian carcinoma group,(53.84± 14.68)pmol/L,(44.25±45.81)U/mL,(10.80± 6.75) ％ in the ovarian benign tumor group,and (46.03±10.26)pmol/L,(17.39±10.64)U/mL,(6.92±3.85)％ in the health control group respectively,compared with the benign tumor group and the health control group,the ovarian carcinoma group were higher in HE4,CA125 and the ROMA value,and the difference were significantly (P＜0.05),whereas compared in the ovarian benign group and the health group,except the CA125 was higher in the benign group and the difference had statistical significance(P＜0.05),the HE4 level and the value of the ROMA had no statistical significance(P＞0.05).The sensitivities of the HE4,CA125 and ROMA were 71.43％,76.79 ％,89.28％,the specificities were 93.15 ％,53.42％,94.52 ％ and the ROC-AUCs were 0.930,0.809,0.937 respectively.When the specificity for the diagnosis of the ovarian carcinoma was 95.00％,the sensitivities of the HE4,CA125 and ROMA were 80.40％,53.60％,83.90％ respectively.Conclusion HE4 and CA125 combined detection to calculate the ROMA can elevate the sensitivity and specificity for the ovarian carcinoma diagnosis.

Analysis of falsely elevated risk of ovarian malignancy algorithm in women with ovarian endometrioma

OBJECTIVE: To estimate the incidence of falsely elevated risk of ovarian malignancy algorithm (ROMA) in a group of women with pathologically confirmed endometrioma and to investigate the associated factors. METHODS: One hundred premenopausal women surgically diagnosed with ovarian endometrioma were selected. Preoperative clinical, laboratory, and surgical characteristics were compared between the elevated-risk group (ROMA-premenopausal value, ≥7.4%) and normal-risk group (ROMA-premenopausal value, 82.3 U/mL and serum level of human epididymis protein 4 (HE4) >46 pmol/L could predict an elevated ROMA test with a statistical significance. When serum level of HE4 ≤46 pmol/L, none of the women showed an elevated ROMA test, regardless of serum level of CA 125; however, 55.6% of the women showed an elevated ROMA test when serum level of HE4 >46 pmol/L and CA 125 ≤82.3 U/mL and all women showed an elevated ROMA test when serum level of HE4 >46 pmol/L and CA 125 >82.3 U/mL. CONCLUSION: The incidence of falsely elevated ROMA was 15% in the group of women with pathologically confirmed endometrioma. Interpretation of the ROMA results should be cautious when serum level of HE4 >46 pmol/L and CA 125 >82.3 U/mL in women with suspicious ovarian endometrioma.

Human Epididymis Protein 4 as a Diagnostic Marker of Ovarian Cancer and Its Reference Interval in Korean Population

Human epididymis protein 4 (HE4), which complements cancer antigen 125 (CA125), has emerged as a new diagnostic biomarker that can discriminate between benign and malignant ovarian tumors. The risk of ovarian malignancy algorithm (ROMA) incorporates CA125, HE4, and menopausal status to classify patients with pelvic masses into those at high or low risk of developing ovarian cancer. The reference interval of HE4 among Korean population was different from those recommended by the manufacturer or evaluated in the Chinese.

Evaluation of ovarian cancer biomarkers HE4 and CA-125 in women presenting with a suspicious cystic ovarian mass / 부인종양

OBJECTIVE: Women presenting with a large or complex ovarian cyst are referred to extensive surgical staging to ensure the correct diagnosis and treatment of a possible epithelial ovarian cancer. We hypothesized that measurement of the biomarkers HE4 and CA-125 preoperatively would improve the assignment of these patients to the correct level of care. METHODS: Patients diagnosed with a cystic ovarian mass and scheduled for an operation at our center of excellence for ovarian cancer surgery from 2001 to 2010 were prospectively included (n=394) and plasma was collected consecutively. Cut-off for HE4 was calculated at 75% specificity (85 pM and 71.8 pM for post and premenopausal women). For CA-125, 35 U/mL cut-off was used. The study population included women with malignant (n=114), borderline (n=45), and benign (n=215) ovarian tumors. RESULTS: Receiver operator characteristic (ROC) area under the curve (AUC) in the benign versus malignant cohorts was 86.8% for CA-125 and 84.4% for HE4. Negative predictive value was 91.7% when at least one of the biomarkers was positive, with only early stage epithelial ovarian cancer showing false negative results. Sensitivity at set specificity (75%) was 87% for risk of ovarian malignancy algorithm (ROMA) in the postmenopausal cohort (cut-off point, 26.0%) and 81% in the premenopausal cohort (cut-off point, 17.3%). ROC AUC in the benign versus stage I epithelial ovarian cancer was only 72% for HE4 and 76% for CA-125. CONCLUSION: In our study, population HE4 did not outperform CA-125. Based on our data a prospective trial with patients already diagnosed with an ovarian cyst may be conducted.