Eur Respir Mon, 2009, 44, 392–406.
Mesothelin is a glycoprotein expressed on the cell surface of normal mesothelial cells, highly overexpressed in mesothelioma and various carcinomas. Soluble mesothelin (SM; or SM-related peptides (SMRP)) has emerged as a promising potential biomarker for MPM. SM levels were greatly increased in the serum and in the pleural effusions of patients with MPM compared with healthy asbestos-exposed subjects or patients with BPL or pleural metastasis. Serum and pleural fluid SM showed excellent sensitivity (70–80%) and specificity (80–100%) as diagnostic markers for MPM. However, SM does not capture sarcomatoid (and some biphasic) mesotheliomas. This fact hampers using SM as a sole diagnostic marker. Combining other potential MPM markers such as osteopontin or CA125 assessment with SM was not helpful in this goal. In asbestos-exposed subjects, it has been suggested that elevated serum SM may predict the later development of MPM, reflecting the presence of undetectable small foci of mesothelioma and preceding clinical disease presentation. The association of pleural abnormalities and high SMRP level in these subjects should be ‘‘aggressively’’ managed to exclude mesothelioma or metastatic malignancies, or at least attempt ‘‘early’’ identification. Such a strategy would need to be validated by prospective trials. At present, mesothelioma cannot meet the essential criteria for cancer screening programmes: there is no validated screening tool or effective cure for MPM, and no evidence that early detection alters outcome. However, detecting mesothelioma years before its clinical presentation may allow testing of new therapeutic approaches in early-stage patients. Thus, studies assessing SM alone or combined with other potential biomarkers for MPM diagnosis or screening are ongoing. Currently, SM remains the best candidate biomarker for MPM diagnosis.