Osteopontin: a useful biomarker in asbestos-related cancer

Pleural mesothelioma is an asbestos-related cancer that invades the chest cavity and the lining of the lungs. Workers at risk for high levels of exposure are miners, factory workers, carpenters, electricians, ship fitters, ships' electricians, boilermakers, insulation manufacturers, railroad workers, gas-mask manufacturers, and pipe insulators.

Recently, a study, published in the October 13 issue of New England Journal of Medicine, was conducted to test the hypothesis that osteopontin is a useful biomarker in pleural mesothelioma and, more specifically, to compare serum levels of osteopontin in a cohort of subjects with asbestos-related biomarker disease with preoperative levels in patients with surgically treated pleural mesothelioma. Osteopontin is a glycoprotein that is over expressed in lung, breast, colorectal, gastric, and ovarian cancer and in melanoma. High levels of osteopontin have previously been shown to correlate with tumor invasion, progression, and metastases.

The researchers investigated the presence of osteopontin in pleural mesothelioma and determined serum osteopontin levels in three populations: subjects without cancer who were exposed to asbestos, subjects without cancer who were not exposed to asbestos, and patients with pleural mesothelioma who were exposed to asbestos.

For the study, a group of 69 subjects with asbestos-related nonmalignant pulmonary disease were compared with 45 subjects without exposure to asbestos and 76 patients with surgically staged pleural mesothelioma. Tumor tissue was examined for osteopontin by immunohistochemical analysis, and serum osteopontin levels were measured by an enzyme-linked immunosorbent assay.

Serum osteopontin levels were found to be significantly higher in the group with pleural mesothelioma than in the group with exposure to asbestos. Immunohistochemical analysis revealed osteopontin staining of the tumor cells in 36 of 38 samples of pleural mesothelioma.

Data from this study suggest that serum osteopontin levels could be used to discriminate between persons with exposure to asbestos who do not have early pleural mesothelioma and those with exposure to asbestos who do have early pleural mesothelioma, regardless of the histologic type of the mesothelioma.

The authors point out that the most important result of this study is the apparent ability of an enzyme-linked immunosorbent assay (ELISA) for osteopontin to identify early pleural mesothelioma (stage I). Also, the finding that osteopontin was present in the tumor cells of pleural mesothelioma and not in the stroma provides support for the specificity of osteopontin as a marker for transformed mesothelial cells. This finding, if confirmed, would have immediate clinical applications, because the use of therapy could potentially influence survival among patients with stage I pleural mesothelioma.