Serum Mesothelin for Early Detection of Asbestos-Induced Cancer Malignant Mesothelioma

Malignant mesothelioma is an aggressive, almost uniformly fatal tumor, primarily caused by exposure to asbestos. Since the recent discovery that serum mesothelin is a sensitive and highly specific biomarker for mesothelioma, one of the key issues raised is whether mesothelin levels represent a usefu...

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Bibliographic Details
Published in:Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2010-09, Vol.19 (9), p.2238-2246
Main Authors: CREANEY, Jenette, OLSEN, Nola J, BRIMS, Fraser, DICK, Ian M, MUSK, Arthur W, DE KLERK, Nicholas H, SKATES, Steven J, ROBINSON, Bruce W. S
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Asbestos - adverse effects
Biological and medical sciences
Biomarkers, Tumor - blood
Case-Control Studies
Early Detection of Cancer - methods
Female
GPI-Linked Proteins - blood
Humans
Male
Medical sciences
Membrane Glycoproteins - blood
Mesothelioma - blood
Mesothelioma - etiology
Mesothelioma - pathology
Middle Aged
Retrospective Studies
Tumors
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Summary:Malignant mesothelioma is an aggressive, almost uniformly fatal tumor, primarily caused by exposure to asbestos. Since the recent discovery that serum mesothelin is a sensitive and highly specific biomarker for mesothelioma, one of the key issues raised is whether mesothelin levels represent a useful screening test for asbestos-exposed at-risk individuals. In this study, soluble mesothelin was determined in sequential serum samples collected from asbestos-exposed individuals before the development of mesothelioma. Archival serum samples from 106 individuals who developed mesothelioma, 99 asbestos-exposed individuals from the Wittenoom Cancer Surveillance Program, and 109 non-asbestos-exposed individuals from the Busselton Health Survey were identified. Serum mesothelin concentrations were determined using the MESOMARK assay. Longitudinal mesothelin levels determined in healthy asbestos-exposed individuals over a period of 4 years were stable (Pearson's r = 0.96; P < 0.0001). There was no correlation between mesothelin concentration and cumulative asbestos exposure. Mesothelin concentrations were greater than the threshold value of 2.5 nmol/L in the penultimate serum sample before the diagnosis of mesothelioma in 17 of 106 people. Using an increase above the 95% confidence interval of the mean of a given individual's longitudinal mesothelin results, 33 of 82 individuals had increasing mesothelin levels before diagnosis. In a population with a high pretest probability of developing mesothelioma, the serum biomarker mesothelin is elevated in absolute terms in 15% and in relative terms in 40% of the group. Future studies examining a combination of biomarkers could improve sensitivity of screening.
ISSN:1055-9965
1538-7755
DOI:10.1158/1055-9965.epi-10-0346