Mesothelin-family proteins: a novel diagnostic marker for malignant mesothelioma?

The pathological diagnosis of malignant mesothelioma (MM) remains difficult and special immunohistochemistry based stains are often required. This paper describes the role of mesothelin—a cell surface protein—and related soluble proteins in the diagnosis and monitoring of MM. The serum concentration of soluble mesothelin related proteins (SMR) was measured by sandwich ELISA in 44 patients with histologically proven MM, 68 (including 40 with history of exposure to asbestos) matched healthy controls, and 160 patients with inflammatory or malignant disorders of the lung and/or pleura.

37 of 44 patients with MM (84%) had a raised concentration of SMR compared with asbestos exposed (p = 0.0003) and non-asbestos exposed controls (p = 0.0002). Seven of the 40 asbestos exposed controls had a raised level of SMR, three of whom developed mesothelioma within 1–5 years. Only three of the 160 patients with non-MM pleural/lung pathology (one each with cryptogenic fibrosing alveolitis, asbestosis, and NSCLC) had a raised concentration of SMR. None of the seven patients with lung adenocarcinoma had increased levels of SMR. The serum concentration of SMR at the time of diagnosis did not correlate with patient survival, but SMR concentrations correlated with tumour size and disease progression.

These data indicate that the concentration of SMR may be a sensitive early marker for the diagnosis of MM, particularly of the epithelioid variety, and may prove to be a useful screening tool in monitoring at risk individuals exposed to asbestos. Further studies are required to determine the prognostic importance of SMR and to determine the specificity of the assay in diagnosing mesothelioma.