MESOMARK (TM): A potential test for malignant pleural mesothelioma

Research and Development Division, Fujirebio Diagnostics, Inc., Malvern, PA 19355, USA.
Clinical Chemistry (Impact Factor: 7.77). 05/2007; 53(4):666-72. DOI: 10.1373/clinchem.2006.079327
Source: PubMed

ABSTRACT Soluble mesothelin-related peptides (SMRP)have been reported to be potential biomarkers for malignant pleural mesothelioma (MPM). We report analytical and preliminary clinical studies of MESOMARK, a quantitative assay for SMRP.
The MESOMARK assay is a 2-step immunoenzymatic assay in an ELISA format with a 6-point calibration curve (0-32 nmol/L). We assessed analytical imprecision, analyte stability, and analytical interferences. We measured SMRP by this assay in 409 apparently healthy individuals (reference interval study), 177 patients with nonmalignant conditions, and 500 cancer patients, including 88 with MPM.
The limit of detection was 0.16 nmol/L. At 2-19 nmol/L, intraassay imprecision (CV) was 1.1%-5.3%, and total imprecision was 4.0%-11.0%. The mean dilution recovery for 5 samples was 109% (range, 99%-113%). No interference was seen from added bilirubin (200 mg/L), hemoglobin (500 mg/L), triglycerides (30 g/L), chemotherapeutic agents, or other tested substances. Recombinant mesothelin was stable in serum upon freeze/thaw at -70 degrees C and upon storage for at least 7 days at 2-8 degrees C. The 99(th) percentile of the reference group was 1.5 nmol/L [95% confidence interval (CI), 1.2-1.6 nmol/L; n = 409], and mean SMRP was significantly higher in sera from patients with MPM (7.5 nmol/L; 95% CI, 2.8-12.1 nmol/L; n = 88). SMRP was increased in 52% and 5% of MPM patients and asbestos-exposed individuals, respectively. Concentrations in other nonmalignant and malignant conditions were similar to those in healthy controls.
The MESOMARK assay is analytically robust and may be useful for the detection and management of mesothelioma.

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    ABSTRACT: Background Malignant mesothelioma (MM) carries a poor prognosis and response rates to palliative chemotherapy remain low. Identifying patients with MM that are unlikely to respond to chemotherapy could prevent futile treatments and improve patient quality of life. Studies have suggested that soluble mesothelin is a potential biomarker for early diagnosis and prognosis of MM. We set out to explore the utility of serum mesothelin in routine clinical practice. Methods We conducted a prospective exploratory study of serum mesothelin levels in 53 consecutive patients with MM at our institution between April 2009 and February 2011. Survival was assessed and analysed by mesothelin level as both continuous and categorical variables using Cox regression models. Differences in response rate between treatment groups were assessed by the Kruskal-Wallis Test. Results All 53 patients, who had been given study information agreed to participate. The patients’ median age was 69 (range 24–90). Median mesothelin level was 2.7 nM and this value was used to dichotomize categories: ≤2.7 nM (low) and >2.7 nM (high). The progression free survival (PFS) for low vs high mesothelin was 8.0 vs 5.1 months (HR 1.8, p-0.058). When mesothelin was accessed as a continuous variable for PFS the HR was 1.03 (95% CI: 1.01 - 1.06; p = 0.013). The overall survival (OS) for low vs high mesothelin was 17.2 vs 11.3 months (HR 1.9, p = 0.088). When mesothelin was assessed as a continuous variable for OS the HR was 1.02 (95% CI: 0.99 - 1.04; p = 0.073). Thirty patients received chemotherapy of which 18 had a pre-chemotherapy serum mesothelin level. In these 18 patients, the pre-chemotherapy mesothelin level did not correlate with response. Conclusions A single random sample provides information about patient prognosis but does not predict treatment response. We suggest further prospective validation of mesothelin testing as a prognostic biomarker.
    BMC Cancer 09/2014; 14(1):674. DOI:10.1186/1471-2407-14-674 · 3.32 Impact Factor
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    ABSTRACT: For the detection of malignant mesothelioma no single biomarker with reasonable sensitivity and specificity has been described so far. Mesothelin, the most prominent blood-based biomarker, is characterized by high specificity but low sensitivity. It might be reasonable to combine biomarkers of different molecular classes in order to improve the overall performance. The aim of this study was to assess the performance of the combination of mesothelin and miR-103a-3p as blood-based biomarker for mesothelioma. Mesothelin concentration in plasma and miR-103a-3p levels in the cellular blood fraction were analyzed in 43 male mesothelioma patients and 52 male controls formerly exposed to asbestos. For the discrimination of epithelioid and biphasic mesothelioma from asbestos-exposed controls mesothelin and miR-103a-3p showed 74% and 89% sensitivity and 85% and 63% specificity, respectively. For the combination of mesothelin and miR-103a-3p a sensitivity of 95% and a specificity of 81% were calculated. The results of this study show that the combination of mesothelin and miR-103a-3p improves the diagnostic performance of individual blood-based biomarker to detect malignant mesothelioma. The obtained results indicate that the use of biomarkers of different molecular classes might be a reasonable approach to assemble a biomarker panel.
    PLoS ONE 12/2014; 9(12):e114483. DOI:10.1371/journal.pone.0114483 · 3.53 Impact Factor
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    ABSTRACT: Malignant mesothelioma (MM) is a highly aggressive tumor associated with asbestos exposure. The identification of a marker specific for MM may be of considerable value for the early detection of this tumor and may be used in particular to screen groups with a history of asbestos exposure. The aim of this study was to evaluate serum soluble mesothelin-related peptide (SMRP) levels as a diagnostic marker for MM and investigate whether its diagnostic value is enhanced by combination with other biomarkers. Serum SMRP levels were measured using a quantitative enzyme-linked immunosorbent assay in 96 patients with MM, 55 patients with lung cancer and 39 individuals with a history of asbestos exposure. Receiver operating characteristic curves were constructed for performance evaluation. Stepwise logistic regression analysis was used to select marker combinations (MCs). Serum SMRP levels in patients with MM were significantly higher compared to those in the other groups (P<0.001). The sensitivity of SMRP levels in diagnosing MM was 56% and its specificity for MM vs. lung cancer and individuals with asbestos exposure was 87 and 92%, respectively. The area under the curve (AUC) was 0.76 [95% confidence interval (CI): 0.68-0.83] for the differentiation between MM and lung cancer and 0.78 (95% CI: 0.71-0.86) for the differentiation between MM and individuals with asbestos exposure. For the MC of presence of effusion, SMRP and carcinoembryonic antigen (CEA) levels, the AUC for the differentiation between MM and lung cancer (0.92; 95% CI: 0.88-0.97) and the differentiation between MM and individuals with asbestos exposure (0.93; 95% CI: 0.87-1.0) was significantly higher compared to that for SMRP alone (P=0.0001 and 0.0058, respectively). While the specificity of this MC was comparable to SMRP alone, its sensitivity was ∼20% higher compared to that of SMRP alone. Therefore, combining SMRP and CEA improves the diagnostic performance of SMRP alone. A combination of serum biomarkers, including SMRP, may facilitate the non-invasive diagnosis of MM.
    Molecular and Clinical Oncology 11/2013; 1(6):942-948. DOI:10.3892/mco.2013.175


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