Influence of Ovarian Cancer Risk Status on the Diagnostic Performance of the Serum Biomarkers Mesothelin, HE4, and CA125

University of Washington, Seattle, WA 98195, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 06/2009; 18(5):1365-72. DOI: 10.1158/1055-9965.EPI-08-1034
Source: PubMed


To evaluate the effect of ovarian cancer risk on the performance of the serum biomarkers mesothelin, human epididymis protein 4 (HE4), and CA125.
We measured mesothelin, HE4, and CA125 levels from women with invasive ovarian cancer (n = 143), benign gynecologic conditions (n = 124), and controls (n = 344). Demographic, epidemiologic, reproductive, medical, and family history data were collected using a standardized questionnaire. Pedigree and BRCA 1/2 test results were used to stratify women into average and high-risk groups. The diagnostic accuracy of each biomarker was characterized using receiver operating characteristic curve methods.
Baseline characteristics did not vary by risk or case status. The distribution of stage and histology was similar in average and high-risk women. All three markers discriminated ovarian cancer cases from risk-matched healthy and benign controls. Marker performance did not vary by risk status. The sensitivity at 95% specificity for discriminating cases from risk-matched healthy control women in the average and high-risk groups, respectively, was 53.9% and 39.0% for mesothelin, 80.4% and 87.8% for HE4, and 79.4% and 82.9% for CA125. The performance of the markers was not as robust when cases were compared with benign controls. Area under the curve values for cases versus healthy and benign controls did not vary by risk status.
The ability of serum mesothelin, HE4, and CA 125 levels to discriminate ovarian cancer cases from healthy and benign controls is not influenced by risk status. Our findings support the pursuit of additional studies evaluating the early detection potential of these markers in high-risk populations.

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Available from: M. Robyn Robyn Andersen
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    • "Many potential biomarkers have been identified or used during last procedure for diagnostics of ovarian cancer patients [5,6]. Different types of proteins other than commonly accepted and used tumor marker - CA125 (carbohydrate antigen 125) [7-9] or a new biomarker - HE4 (human epididymis protein 4) [9,10] such as cytokines (M-CSF, IL-6) [11-14], and metalloproteinases are currently investigated [15-17]. "
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    ABSTRACT: VEGF may play a role in the pathogenesis of cancer disease, for example in cell growth, proliferation and angiogenesis. In this study, we investigated plasma levels of this cytokine in comparison to plasma levels of a new biomarker - HE4 and the established tumor marker CA125 in ovarian cancer patients (100) as compared to control groups: patients with a benign ovarian tumor (80) and healthy subjects (50). Plasma levels of VEGF were determined by ELISA, HE4 and CA125 by CMIA method. The results showed that levels of VEGF, CA125 and HE4 were significantly higher in ovarian cancer (OC) patients as compared to the both control groups. VEGF has demonstrated as high as comparative markers values of the diagnostic sensitivity (SE), specificity (SP), the predictive values of positive and negative test results (PV-PR, PV-NR), and the area under the ROC curve (AUC) in early stages of cancer tested groups. The combined use of parameters studied resulted in the increase in the diagnostic criteria values and the AUC. These findings suggest the usefulness of VEGF in the early diagnostics of ovarian cancer, especially in combination with CA125 and HE4, as a new biomarkers panel. Additionally, VEGF is the most useful tool in the diagnostics of locally advanced ovarian cancer without metastases. Investigated cytokine presented similar to HE4 usefulness in differentiation of OC according to its histopathlogical sub-type, and could be used especially in the diagnostics of endometrioid epithelial OC.
    Full-text · Article · Jul 2013 · Journal of Ovarian Research
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    • "However, the usefulness of CA125 as a marker cannot be extended to diagnosis as 20% of ovarian cancers do not express CA125 [1], and elevated levels are detected in only half of early stage patients. Further, CA125 is detected in many benign gynecological conditions and is particularly unreliable in detecting ovarian cancer in premenopausal women [2-5]. Additional biomarkers with high sensitivity and specificity for detecting ovarian cancer in the early stages of the disease are sought to complement CA125. "
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    ABSTRACT: Background Evaluate and compare the utility of serum folate receptor alpha (FRA) and megakaryocyte potentiating factor (MPF) determinations relative to serum CA125, mesothelin (MSLN) and HE4 for the diagnosis of epithelial ovarian cancer (EOC). Methods Electrochemiluminescent assays were developed for FRA, MSLN and MPF and used to assess the levels of these biomarkers in 258 serum samples from ovarian cancer patients. Commercial assays for CA125 and HE4 were run on a subset of 176 of these samples representing the serous histology. Data was analyzed by histotype, stage and grade of disease. A comparison of the levels of the FRA, MSLN and MPF biomarkers in serum, plasma and urine was also performed in a subset of 57 patients. Results Serum and plasma levels of FRA, MSLN and MPF were shown to be highly correlated between the two matrices. Correlations between all pairs of markers in 318 serum samples were calculated and demonstrated the highest correlation between HE4 and MPF, and the lowest between FRA and MPF. Serum levels of all markers showed a dependence on both stage and grade of disease. A multi-marker logistic regression model was developed resulting in an AUC=0.91 for diagnosis of serous ovarian cancer, a significant improvement over the AUC for any of the individual markers, including CA125 (AUC=0.84). Conclusions FRA has significant potential as a biomarker for ovarian cancer, both as a stand-alone marker and in combination with other known markers for EOC. The lack of correlation between the various markers analyzed in the present study suggests that a panel of markers can aid in the detection and/or monitoring of this disease.
    Full-text · Article · Apr 2013 · Journal of Ovarian Research
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    • "All of them include the determination of CA125, which however is known to have some flaws such as low sensitivity in early stages, and increases due to benign diseases, especially in pre-menopausal women. Among the new markers recently proposed, HE4 has been quite extensively studied: in particular it seems to be more specific than CA125 [32] [33] [34] and to be increased also in 50% of ovarian cancer patients who do not express CA125 [35]. The ROMA index is a specific algorithm, recently proposed, which incorporates the results of CA125 and HE4 and takes into account the menopausal status. "
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    ABSTRACT: Objective: The quality of first surgery is one of the most important prognostic factors in ovarian cancer patients. Pre-surgical distinction of benign and malignant pelvic mass plays a critical role in ovarian cancer management and survival. The aim of this study was to evaluate the clinical performance of ROMA algorithm and of CA125 and HE4 in the triage of patients with a pelvic mass undergoing surgery, in order to discriminate benign from malignant disease. Methods: Three hundred and forty-nine pre- and post-menopausal women, aged 18 years or older undergoing surgery because of a pelvic mass were enrolled: serum concentrations of CA125 and HE4 were determined and ROMA was calculated for each sample. Results: Median serum CA125 and HE4 levels were higher in patients with EOC compared to subjects with benign disease (p<0.0001). The resultant accuracy (using Receiver Operating Characteristics, ROC Area) values for HE4, CA125 and ROMA showed a good performance ranging from 89.8% for CA125 in pre-menopausal patients to 93.3% for ROMA in post-menopausal patients: AUC for ROMA resulted significantly higher in comparison to CA125 alone (93.3% vs 90.3%, p=0.0018) in post menopausal patients. A sub-analysis considering the 40 patients with endometrioid disease showed the highest accuracy of HE4 in these patients. Conclusions: Data presented confirm the accuracy of HE4 and of the ROMA algorithm in the distinction of ovarian carcinoma from benign disease, with a trend towards better performance for ROMA than for CA125 alone, statistically significant in postmenopausal patients.
    Full-text · Article · Nov 2012 · Gynecologic Oncology
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