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Clinical Significance of Serum Mesothelin in Patients with Mesothelioma and Lung Cancer

Authors' Affiliations: ¹ Department of Endocrinology and Metabolism, Orthopaedics and Traumatology, Occupational Medicine, University of Pisa, ² Pulmonary Unit, University Hospital of Pisa, Pisa, Italy; ³ Molecular Epidemiology, ⁴ Clinical Pathology, and ⁵ Epidemiology and Biostatistics, National Cancer Research Institute of Genoa, ⁶ Pulmonary Unit, ⁷ Medical Oncology, A.O. Villa Scassi Genoa, Genoa, Italy; ⁸ Pulmonary Unit, A.O. Sarzana, La Spezia, Italy; and ⁹ Department of Medicine, Local Health Unit 11, Vercelli, Italy

Requests for reprints: Alfonso Cristaudo, Departments of Endocrinology and Metabolism, Orthopaedics and Traumatology, and Occupational Medicine, University of Pisa, "Cisanello Hospital", Via Paradisa 2, Pisa 56124, Italy. Phone: 39-5099-3820; Fax: 39-5099-3822; E-mail: a.cristaudo{at}med.unipi.it.

Purpose: High levels of serum-soluble mesothelin family proteins (SMRP) have been found to be associated with malignant mesothelioma (MM), but not lung cancer (LC). To verify the clinical role of this marker for both these tumors, we tested serum SMRP in the largest population of thoracic cancers ever assembled.

Experimental Design: SMRP blood concentrations were measured in 107 patients with MM, 215 patients with LC, 130 patients with benign respiratory diseases (BRD), and 262 controls. Statistical comparison between mean serum SMRP levels in all groups was done and receiver operating characteristic curves were constructed to evaluate the performance of this marker.

Results: SMRP levels were significantly higher in patients with MM and LC than in patients with benign respiratory diseases and controls (P < 0.001). The area under the receiver operating characteristic curve for serum SMRP discriminating MM and controls was 0.77 (95% confidence interval, 0.71-0.83), with a best cutoff of 1.00 nmol/L (sensitivity, 68.2%; specificity, 80.5%). In both MM and LC, serum SMRP levels did not differ significantly between early and late stages. High SMRP levels proved to be an independent negative prognostic factor in patients with MM.

Conclusions: Our data confirm that serum SMRP is a promising marker for the diagnosis, prognosis, and clinical monitoring of MM. We found that serum SMRP dosage may prove helpful in LC diagnosis as well. These data may also have positive repercussions on secondary preventive medical strategies for workers previously exposed to asbestos.