title: Clinical impact and reliability of pleural fluid mesothelin in undiagnosed pleural effusions.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Oxford Centre for Respiratory Medicine, University of Oxford, Oxford, UK.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Davies
authors.forename: Ross S
authors.initials: RS
authors.lastname: Sadler
authors.forename: Silvia
authors.initials: S
authors.lastname: Bielsa
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Maskell
authors.forename: Najib M
authors.initials: NM
authors.lastname: Rahman
authors.forename: Robert J O
authors.initials: RJ
authors.lastname: Davies
authors.forename: Berne L
authors.initials: BL
authors.lastname: Ferry
authors.forename: Y C Gary
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000368:Aged; D001424:Bacterial Infections / Q000150:complications / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D000090204:Mesothelin; D008654:Mesothelioma / Q000150:complications / Q000175:diagnosis; D010996:Pleural Effusion / Q000209:etiology / Q000378:metabolism*; D016066:Pleural Effusion, Malignant / Q000209:etiology / Q000378:metabolism / Q000628:therapy; D018700:Pleurodesis; D011446:Prospective Studies; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D000090204:Mesothelin