Mesothelin-family proteins and diagnosis of mesothelioma.
BACKGROUND
Mesothelioma is a highly aggressive tumour for which there are no reliable serum tumour markers. Identification of such a marker would be useful in diagnosis of mesothelioma and for monitoring responses to treatment and screening at-risk individuals.


METHODS
We assayed serum concentrations of soluble mesothelin-related proteins (SMR) using a double determinant (sandwich) ELISA in a blinded study of serum samples from 44 patients with histologically proven mesothelioma; 68 matched healthy controls, 40 of whom had been exposed to asbestos; and 160 patients with other inflammatory or malignant lung and pleural diseases.


RESULTS
37 (84%) of 44 patients with mesothelioma had raised concentrations of SMR at a serum dilution of 1/80, compared with three (2%) of 160 patients with other cancers or other inflammatory lung or pleural diseases, and with none of 28 controls who had not been exposed to asbestos. SMR concentrations correlated with tumour size and increased during tumour progression. Seven of the 40 asbestos-exposed individuals had increased serum concentrations of SMR; three of those seven developed mesothelioma and one developed lung carcinoma within 1-5 years. None of the 33 asbestos-exposed participants whose serum samples had normal concentrations of SMR and who were followed up over 8 years developed mesothelioma.


CONCLUSIONS
Determination of SMR in serum could be a useful marker for diagnosis of mesothelioma and to monitor disease progression. It might also prove helpful for screening asbestos-exposed individuals for early evidence of mesothelioma.
Robinson
Bruce W S
BW
University Department of Medicine, University of Western Australia, Queen Elizabeth II Medical Centre, Western Australia, Perth, Australia. bwsrobin@cyllene.uwa.edu.au
Creaney
Jenette
J
Lake
Richard
R
Nowak
Anna
A
Musk
A William
AW
de Klerk
Nick
N
Winzell
Pernilla
P
Hellstrom
Karl Erik
KE
Hellstrom
Ingegerd
I
D000951:Antigens, Neoplasm / Q000097:blood*; D001194:Asbestos; D014408:Biomarkers, Tumor / Q000097:blood*; D004781:Environmental Exposure; D058851:GPI-Linked Proteins; D006801:Humans; D008171:Lung Diseases / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood; D008562:Membrane Glycoproteins / Q000097:blood*; D000090204:Mesothelin; D008654:Mesothelioma / Q000097:blood* / Q000175:diagnosis; D010995:Pleural Diseases / Q000097:blood; D010997:Pleural Neoplasms / Q000097:blood*
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D001194:Asbestos; D000090204:Mesothelin