Serum mesothelin for early detection of asbestos-induced cancer malignant mesothelioma.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.


CONCLUSIONS
Future studies examining a combination of biomarkers could improve sensitivity of screening.
Creaney
Jenette
J
National Research Centre for Asbestos Related Disease, Sir Charles Gairdner Hospital, 2School of Medicine and Pharmacology, University of Western Australia, QEII Medical Centre, Nedlands, Western Australia, Australia. creaneyj@cyllene.uwa.edu.au
Olsen
Nola J
NJ
Brims
Fraser
F
Dick
Ian M
IM
Musk
Arthur W
AW
de Klerk
Nicholas H
NH
Skates
Steven J
SJ
Robinson
Bruce W S
BW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001194:Asbestos / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D000090204:Mesothelin; D008654:Mesothelioma / Q000097:blood* / Q000209:etiology* / Q000473:pathology; D008875:Middle Aged; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D001194:Asbestos; D000090204:Mesothelin