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Clinical Impact and Reliability of Pleural Fluid Mesothelin in Undiagnosed Pleural Effusions

¹ Oxford Centre for Respiratory Medicine and University of Oxford, Oxford; ² Department of Clinical Immunology, Churchill Hospital, Oxford; ³ Centre for Respiratory Research, University College London, London; and ⁴ University of Bristol and Southmead Hospital, Bristol, United Kingdom

Correspondence and requests for reprints should be addressed to Y. C. Gary Lee, Ph.D., University Department of Medicine and Lung Institute of Western Australia, University of Western Australia, G Block, 4/F, QE II Med Ctr, Perth WA6009, Australia. E-mail: gary.lee{at}uwa.edu.au

Rationale: Serum mesothelin is a new biomarker for the diagnosis of mesothelioma. Patients with mesothelioma commonly present with pleural effusions. To define the clinical utility of mesothelin quantification in pleural fluid, we assessed its additional value over pleural fluid cytology and its short-term reproducibility and reliability after pleural inflammatory processes, including pleurodesis.

Objectives: To assess the diagnostic role of pleural fluid mesothelin and the effect of common clinical factors that may influence measurement accuracy.

Methods: Mesothelin was quantified in 424 pleural fluid and 64 serum samples by ELISA. Fluid was collected prospectively from 167 patients who presented with pleural effusions for investigation. Serial pleural fluid samples were obtained from patients (n = 33) requiring repeated drainage. Mesothelin levels were also measured in patients (n = 32) prepleurodesis and postpleurodesis.

Measurements and Main Results: Pleural fluid mesothelin concentrations were significantly higher in patients with mesothelioma (n = 24) relative to those with metastatic carcinomas (n = 67) and benign effusions (n = 75): median (interquartile range, 25th–75th percentile) = 40.3 (18.3–68.1) versus 6.1 (1.5–13.2) versus 3.7 (0.0–12.4) nM, respectively, P < 0.0001. Mesothelin measurement was superior to cytological examination in the diagnosis and exclusion of mesothelioma (sensitivity, 71 vs. 35%; specificity, 89 vs. 100%; negative predictive value, 95 vs. 82%, respectively). In patients with "suspicious" cytology, pleural fluid mesothelin was 100% specific for mesothelioma, and in cytology-negative effusions (n = 105) offered a negative predictive value of 94%. Intraindividual reproducibility of pleural fluid mesothelin was excellent: mean (±SD) variation, –0.15 (±8.41) nM in samples collected within 7 days from patients with mesothelioma. Measurements remained reliable after pleurodesis and were not affected by the presence of bacteria.

Conclusions: Pleural fluid mesothelin provides additional diagnostic value relative to cytological examination. Mesothelin measurements are reproducible and not affected by inflammatory pleural processes.

Key Words: pleural effusion • mesothelin • biomarker • mesothelioma • pleura

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Serum mesothelin is a diagnostic biomarker for mesothelioma. Pleural fluid values are significantly higher than serum levels and may offer additional value over pleural fluid cytology for diagnosis of pleural malignancy. The clinical utility of pleural fluid mesothelin has not yet been defined. What This Study Adds to the Field This study demonstrates that pleural fluid mesothelin is a valuable adjunct to cytological examination in patients with an undiagnosed pleural effusion. It is reproducible and not influenced by common inflammatory pleural processes.