JCO Early Release, published online ahead of print Mar 12 2012
Journal of Clinical Oncology, 10.1200/JCO.2011.39.6671

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Serum Mesothelin for Diagnosing Malignant Pleural Mesothelioma: An Individual Patient Data Meta-Analysis

Kevin Hollevoet and Jan P. van Meerbeeck, Ghent University Hospital, Ghent; Kristiaan Nackaerts, University Hospital Gasthuisberg, Leuven, Belgium; Johannes B. Reitsma, University Medical Center Utrecht, Utrecht; Paul Baas, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Jenette Creaney and Bruce W. Robinson, University of Western Australia, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; Bogdan D. Grigoriu, University of Medicine, Iasi, Romania; Arnaud Scherpereel, University Hospital (Centre Hospitalier Régional et Universitaire) of Lille II, Lille, France; Alfonso Cristaudo, University of Pisa, Pisa; Francesca Di Serio, University Hospital, Bari; Marco Tomasetti, Polytechnic University of Marche, Ancona, Italy; José A. Rodríguez Portal, Virgen del Rocío University Hospital, Seville, Spain; Joachim Schneider, Justus-Liebig Universität, Giessen; Thomas Muley, Thoraxklinik am Universitätsklinikum Heidelberg, Heidelberg, Germany; Kevin Hollevoet, National Cancer Institute, National Institutes of Health, Bethesda, MD; Harvey I. Pass, New York University, Langone Medical Center and Cancer Center; and Alex J. Rai, Columbia University Medical Center, New York, NY.

Corresponding author: Kevin Hollevoet, PhD, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Dr, Room 5110, Bethesda, MD 20892-4264; e-mail: kevin.hollevoet{at}nih.gov.

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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