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Among the many challenges of managing mesothelioma are the difficulties in diagnosing and then following the disease for progression or response to treatments administered. One of the potential tools to help in this regard is an assay of soluble mesothelin related peptides, now a commercially available test called Mesomark. Mesothelin is a glycoprotein (a protein with sugar molecules attached to it) that is expressed on normal mesothelial cells but also over-expressed in patients with malignant pleural mesothelioma (MPM) as well as potentially in patients with peritoneal mesothelioma or ovarian cancer. Soluble mesothelin-related peptides (SMRPs) are believed to be either peptide fragments of mesothelin (peptides being pieces of larger proteins) or variant versions of mesothelin that don’t remain bound to the cell surface. These SMRPs can then end up in serum or pleural fluid.
The two main ways in which SMRPs, or the Mesomark assay, might be used is to make the diagnosis of mesothelioma or to follow the course of the disease. What we’ve learned is that while the Mesomark assay shows an abnormal elevation in some patients with mesothelioma, that proportion has varied from 19% to 68% of the patients tested 1, less commonly elevated in patients with earlier stage (I or II) MPM or in the minority of patients with sarcomatoid histology. On the other hand, when the Mesomark assay is found to be elevated in a patient with a suspicion of MPM, the vast majority of the time (88-100% in different studies), the diagnosis was ultimately confirmed. Another approach is to look at SMRP in pleural fluid 2, since patients with MPM are often initially diagnosed after presenting with shortness of breath caused by a large pleural effusion. However, results with pleural fluid are similarly infallible, with a substantial proportion of patients with MPM failing to demonstrate abnormally elevated SMRPs in pleural fluid. At this time, it is appropriate to send blood or potentially pleural fluid for the Mesomark assay, though it is necessary to recognize that an abnormal test does not replace a tissue diagnosis from a biopsy, and also that many patients with MPM will not have an abnormal Mesomark test.
Another setting in which the Mesomark assay could be helpful is for following the course of the disease in patients known to have SMRPs elevated at diagnosis 3. Here, the Mesomark assay serves a similar function as Prostate Specific Antigen, or PSA, another blood test that is controversial in its role for diagnosing cancer, but PSA testing is the most common and readily available way to monitor the course of prostate cancer. Both prostate cancer and MPM are diseases in which imaging is often not especially reliable, as there is often no obviously measurable discrete lesion or collection of lesions to follow on imaging scans. In these situations, having a blood test that can be monitored can be quite helpful. After surgery, where post-operative scarring can make it extremely difficult to interpret scan findings, is the previously elevated Mesomark continuing to remain low, or has it begun to rise after initially dropping after surgery? In the much larger proportion of MPM patients who aren’t candidates for surgery, SMRPs declining over time typically correlate with scan findings, offering an option between scans for monitoring response to often difficult therapy, and potentially providing a more reliable index of activity than imaging when there is extensive scarring after a pleurodesis or other ambiguous scan findings.
While the Mesomark assay isn’t abnormal in enough patients to be a conclusive indicator of mesothelioma in patients who are undergoing an initial workup and are still awaiting a diagnosis, it is now a helpful tool to add for the significant subset of patients who are found to have abnormally elevated SMRPs.
1. Hollevoet K, Reitsma JB, Creaney J, et al. Serum mesothelin for diagnosing malignant pleural mesothelioma: An individual patient data meta-analysis. J Clin Oncol 30: 1541-1549, 2012.
2. Creaney J, Yeoman D, Naumoff LK, et al. Soluble mesothelin in effusions: a useful tool for the diagnosis of malignant mesothelioma. Thorax 62: 569-573, 2007.
3. Wheatley-Price P, Yang B, Patsios D, et al. Soluble mesothelin-related peptide and osteopontin as markers of response in malignant mesothelioma. J Clin Oncol 28: 3316-3322, 2010.