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Soluble Mesothelin–related Peptides in the Diagnosis of Malignant Pleural Mesothelioma

Arnaud Scherpereel^*, Bogdan Grigoriu^*, Massimo Conti, Thomas Gey, Marc Grégoire, Marie-Christine Copin, Patrick Devos, Bachar Chahine, Henri Porte and Philippe Lassalle

INSERM Unit 774, Institut Pasteur de Lille; Departments of Pulmonary and Thoracic Oncology, Thoracic Surgery, and Pathology, University Hospital of Lille; Department of Biostatistics, Medical School of Lille, Lille; INSERM U601, Nantes, France; and University of Medicine, Iasi, Romania

Correspondence and requests for reprints should be addressed to Arnaud Scherpereel, M.D., Ph.D., Clinique des Maladies Respiratoires, Hopital Calmette, CHRU of Lille, 59037 Lille Cedex, France. E-mail: a-scherpereel{at}chru-lille.fr

Background: Diagnosis of malignant pleural mesothelioma is a challenging issue. Potential markers in mesothelioma diagnosis include soluble mesothelin–related peptides (SMRPs) and osteopontin, but no subsequent validation has been published yet.

Methods: We prospectively evaluated SMRPs in serum and pleural effusion from patients with mesothelioma (n = 74), pleural metastasis of carcinomas (n = 35), or benign pleural lesions associated with asbestos exposure (n = 28), recruited when first suspected for mesothelioma.

Findings: Mean serum SMRP level was higher in patients with mesothelioma (2.05 ± 2.57 nM/L [median ± interquartile range]) than in patients with metastasis (1.02 ± 1.79 nM/L) or benign lesions (0.55 ± 0.59 nM/L). The area under the receiver operating characteristic curve (AUC) for serum SMRP was 0.872 for differentiating mesothelioma and benign lesions, cut-off = 0.93 nM/L (sensitivity = 80%, specificity = 82.6%). The AUC for serum SMRP differentiating metastasis and mesothelioma was 0.693, cut-off = 1.85 nM/L (sensitivity = 58.3%, specificity = 73.3%). SMRP values in pleural fluid were higher than in serum in all groups (mesothelioma: 46.1 ± 83.2 nM/L; benign lesions: 6.4 ± 11.1 nM/L; metastasis: 6.36 ± 21.73 nM/L). The AUC for pleural SMRP-differentiating benign lesions and mesothelioma was 0.831, cut-off = 10.4 nM/L (sensitivity = 76.7%, specificity = 76.2%). The AUC for pleural SMRP-differentiating metastasis and mesothelioma was 0.793.

Interpretation: We show that SMRPs may be a promising marker for mesothelioma diagnosis when measured either in serum or pleural fluid. The diagnostic value of SMRPs was similar in both types of samples, but pleural fluid SMRPs may better discriminate mesothelioma from pleural metastasis.

Key Words: diagnosis • marker • neoplasm • pleural disease

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