Serum Mesothelin for diagnosing malignant pleural mesothelioma: an individual patient data meta-analysis

Purpose: Mesothelin is currently considered the best available serum biomarker of malignant pleural mesothelioma. To examine the diagnostic accuracy and use of serum mesothelin in early diagnosis, we performed an individual patient data (IPD) meta-analysis. Methods: The literature search identified...

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Hauptverfasser: Hollevoet, Kevin (VerfasserIn) , Muley, Thomas (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: March 12, 2012
In: Journal of clinical oncology
Year: 2012, Jahrgang: 30, Heft: 13, Pages: 1541-1549
ISSN:1527-7755
DOI:10.1200/JCO.2011.39.6671
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1200/JCO.2011.39.6671
Verlag, Volltext: http://ascopubs.org/doi/10.1200/JCO.2011.39.6671
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Verfasserangaben:Kevin Hollevoet, Johannes B. Reitsma, Jenette Creaney, Bogdan D. Grigoriu, Bruce W. Robinson, Arnaud Scherpereel, Alfonso Cristaudo, Harvey I. Pass, Kristiaan Nackaerts, José A. Rodríguez Portal, Joachim Schneider, Thomas Muley, Francesca Di Serio, Paul Baas, Marco Tomasetti, Alex J. Rai, and Jan P. van Meerbeeck

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520 |a Purpose: Mesothelin is currently considered the best available serum biomarker of malignant pleural mesothelioma. To examine the diagnostic accuracy and use of serum mesothelin in early diagnosis, we performed an individual patient data (IPD) meta-analysis. Methods: The literature search identified 16 diagnostic studies of serum mesothelin, measured with the Mesomark enzyme-linked immunosorbent assay. IPD of 4,491 individuals were collected, including several control groups and 1,026 patients with malignant pleural mesothelioma. Mesothelin levels were standardized for between-study differences and age, after which the diagnostic accuracy and the factors affecting it were examined with receiver operating characteristic (ROC) regression analysis. Results: At a common diagnostic threshold of 2.00 nmol/L, the sensitivities and specificities of mesothelin in the different studies ranged widely from 19% to 68% and 88% to 100%, respectively. This heterogeneity can be explained by differences in study population, because type of control group, mesothelioma stage, and histologic subtype significantly affected the diagnostic accuracy. The use of mesothelin in early diagnosis was evaluated by differentiating 217 patients with stage I or II epithelioid and biphasic mesothelioma from 1,612 symptomatic or high-risk controls. The resulting area under the ROC curve was 0.77 (95% CI, 0.73 to 0.81). At 95% specificity, mesothelin displayed a sensitivity of 32% (95% CI, 26% to 40%). Conclusion: In patients suspected of having mesothelioma, a positive blood test for mesothelin at a high-specificity threshold is a strong incentive to urge further diagnostic steps. However, the poor sensitivity of mesothelin clearly limits its added value to early diagnosis and emphasizes the need for further biomarker research. 
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