Objective: To analyze differential diagnostic accuracy of urinary human epidydimis secretory protein 4 (HE4) in patients with ovarian tumors. Materials and methods: In the case-control study 23 patients with ovarian cancer, 37 patients with benign ovarian tumors and 18 women in the control group were included. Serum CA125 values and urinary concentrations of HE4were assessed quantitatively. Urinary creatinine concentrations and glomerular filtration rate were also determined and used to calculate ratios to HE4. Results: Higher urinary HE4 concentrations were observed in patients with late stage ovarian cancer (p=0.001) and also in patients with early stage ovarian cancer when compared to patients with benign ovarian tumors (p=0.044). On analysis where all ovarian cancer patients were included, higher diagnostic accuracy was observed with calculated ratio of HE4 to glomerular filtration rate (GFR) to unchanged urinary HE4 concentrations -AUC 0.861 vs. 0.858. When discriminatory accuracy was calculated for urinary HE4/GFR ratio and unchanged urinary HE4 concentrations, the last demonstrated a higher area under the curve -0.701 vs. 0.602. The urinary HE4/creatinine ratio had lower discriminatory characteristics than unchanged concentrations of urinary HE4. However, HE4 serum concentration was more accurate for discrimination of patients with benign and malignant ovarian tumors when compared to urinary HE4 and CA125 in sera (AUCs were 0.868 for serum HE4 and 0.856 and 0.653 for urinary HE4 and CA125, respectively). Conclusions: Ovarian cancer patients have higher urinary concentrations of human epidydimis secretory protein 4 than patients with benign ovarian tumors. Urinary HE4 has comparable discriminatory accuracy with serum HE4 for benign and malignant ovarian tumors and can be recommended as a non-invasive ovarian cancer risk assessment method.

A case-control study included 83 ovarian cancer patients, 76 patients with benign ovarian tumors, and 79 healthy control subjects in the control group. Objective of the study is to analyze biomarker concentrations included in the two novel ovarian tumor differential diagnostic tests (risk of ovarian malignancy algorithm and OVA1) approved by food and drug administration in patients with ovarian tumors and to establish a new ovarian cancer risk assessment algorithm in conjunction with ultrasound score and menopausal status. Ovarian cancer diagnostic tests, developed in the training setting, were evaluated in the independent validation settings of Asian Pacific ovarian cancer biomarker research group study population and Denmark Pelvic Mass project population. Results show that mean serum concentrations of cancer antigen 125 (CA125), human epididymis secretory protein 4 (HE4), and beta-2-microglobulin were upregulated, but apolipoprotein A1, transferrin, and transthyretin were downregulated among ovarian cancer patients. When only one biomarker was introduced in the logistic regression analysis, together with ultrasonographic score and menopausal status, HE4 (area under the curve (AUC) = 0.930; 95 % confidence interval (CI) 0.891-0.969) was more accurate than CA125 (AUC = 0.902; 95 % CI 0.855-0.949) in ovarian cancer diagnostic, but when both biomarkers were included in the logistic regression analyses, ovarian cancer diagnostic accuracy was increased (AUC = 0.939; 95 % CI 0.902-0.977). In conclusions, human epididymis secretory protein 4 and CA125 in combination with ultrasonographic features and menopausal status has high accuracy in ovarian tumor differentiation.

SummaryIntroduction. Advanced technologies such as matrix assisted laser desorption/ionization and surface enhanced laser desorption/ ionization mass spectrometry has introduced promising insights into ovarian cancer detection. Several highly sensitive and specific protein peaks have been identified that discriminates ovarian cancer patients from patients with benign ovarian tumors and controls. Aim of the Study. Objective of this study is to evaluate diagnostic accuracy each individual marker and combined serum biomarker assay consisting of apolipoprotein A1, transferrin and Ca125. Materials and methods. A case-control study consisted of 99 women -37 patients with ovarian cancer, 31 patients with benign ovarian diseases, and 31 age-matched healthy controls. Apolipoprotein A1 and transferrin was measured in sera using immunological turbidimetric assay. Tumor marker CA125 was analyzed by standard enzyme-labeled chemiluminescent immunometric assay. To compare the difference between variables in the study groups, ANOVA test was performed and for correlation Pearson's correlation analysis applied. Sensitivity and specificity of the diagnostic tests was calculated using statistical program Vassarstat. Results. Serum apolipoprotein A1 and transferrin were down regulated, controversially to Ca125, which was up regulated among ovarian cancer patients. Negative correlation between transferrin and Ca 125 (p<0.00), apolipoprotein A1 and Ca 125 (p<0.00) and positive correlation between transferrin and apolipoprotein A1 (p<0.00) was observed. For single biomarker test highest diagnostic sensitivity and specificity for Ca125 was observed. Addition of apolipoprotein A1 or transferrin to serum level of Ca125 with the condition, that both have to overlap the threshold (Ca125 > 21U/ml and apolipoprotein A1 ≤139.1 mg/dl or transferrin ≤ 2.3 g/l), yielded test specificity of 96.7%. Addition of apolipoprotein A1 to Ca125 improved test sensitivity up to 94.5% maintaining high sensitivity at the same time 91.1%, respectively, when discriminating controls from ovarian cancer patients. Biomarker test consisting of apolipoprotein A1, transferrin and Ca125 had high specificity at unacceptable sensitivity. Conclusions. Combined biomarker tests discovered using advanced technologies can aid more accurate ovarian cancer detection. Use of apolipoprotein A1 in combination with Ca125 at distinct thresholds can improve ovarian cancer detection.

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Role of a combined soluble interleukine-2 receptor alpha (sIL-R2α) and CA-125 serum marker assay for detection of ovarian cancer Detection of ovarian cancer can be improved using a combined diagnostic test consisting of Ca-125 and serum interleukine-2 receptor alpha (sIL-R2α) at a particular threshold. The objective of the study was to evaluate the accuracy of a diagnostic marker assay that combined Ca-125 and serum interleukine-2 receptor alpha. A case-control study of 38 patients with ovarian cancer, 40 patients with benign ovarian diseases and 31 age-matched healthy controls was designed. Ca-125 and sIL-2Rα were detected in patients' serum by standardized chemiluminescent immunometric assays. For Ca-125, a standard cutoff level of 21 U/ml was applied and for sIL-R2α — two cutoff levels were calculated from women included in the control group — one as a mean concentration and the other as an upper limit of a 95% confidence interval. Mean serum concentrations among ovarian cancer patients for CA125 and sIL-2Rα were 265.9 ± 40.2 U/ml and 651.0 ± 50.5 U/ml, respectively. The upper limit of the 95% confidence interval for a healthy control group of women was 304.5 U/ml for sIL-2Rα. Sensitivity and specificity of 89.4% and 85.9% was achieved when CA125 was combined together with sIL-2Rα at a threshold of 304.5U/ml with the condition that both markers are elevated. Sensitivity and specificity of 92.5% and 88.4% was observed when both biomarkers were applied to menopausal women. Serum sIL-2Rα in combination with CA125 can be used as a differential diagnostic test for ovarian cancer at a specific threshold, especially among menopausal women.