Diagnostic and Prognostic Value of Soluble Mesothelin-Related Proteins in Patients with Malignant Pleural Mesothelioma in Comparison with Benign Asbestosis and Lung Cancer

Abstract

We investigated the diagnostic and prognostic value of soluble mesothelin-related proteins (SMRP) in sera from patients with newly diagnosed malignant pleural mesothelioma (MPM) (n = 100), MPM patients at tumor relapse (n = 29), primary lung cancer (n = 139), and benign asbestosis (n = 75) using Mesomark--enzyme-linked immunosorbent assay kit (Fujirebio Diagnostics, Malvern, PA). SMRP concentrations were significantly higher in MPM compared with benign asbestosis (p < 0.001) or lung cancer (p < 0.001). The median values were 1.4 nM, 0.9 nM, and 0.8 nM, respectively. The best statistical cutoff was found to be 1.35 nM resulting in a sensitivity of 53% and a specificity of 82.7%. Receiver operating characteristics curves gave an area under curve of 0.72 for the discrimination between MPM and non-MPM patients (p < 0.001). No significant differences in SMRP levels were found among histologies and stages of MPM. The highest median SMRP levels (4.2 nM) were measured in 29 MPM patients with relapse/progression (75.8% > 1.35 nM). Univariately, SMRP discriminated significantly (p < 0.003) between favorable (n = 71, median survival: 17.1 month; 1-year survival: 63.1%) and worse prognosis (n = 20, median survival: 8.4 months, 1-year survival: 32%) at 3.5 nM. In multivariate analysis, histology, therapy, and SMRP were shown to be independent prognostic factors in all MPM patients (hazard ratio for SMRP: 1.96; p = 0.025). Nevertheless, subtype-driven reanalysis showed only a trend in epithelial MPM. In conclusion, SMRP add limited information to the diagnosis of MPM. Nevertheless, SMRP might be a useful measure in treatment and monitoring of MPM. The prognostic impact of SMRP in MPM is not conclusive and needs further evaluation.