title: Comparison between plasma and serum osteopontin levels: usefulness in diagnosis of epithelial malignant pleural mesothelioma.
abstract: BACKGROUND
  A potential role of serum osteopontin (OPN) and serum mesothelin-related peptide (SMRP) in the diagnosis of malignant pleural mesothelioma (MPM) has been recently reported. Although the most important data regarding the role of OPN in MPMs derive from the marker's measurement in serum samples, most commercial laboratory kits for OPN assay are suitable only for measuring plasma levels, as indicated by the manufacturers. Our study aimed to evaluate the influence of preanalytic variables on serum and plasma OPN, to compare serum and plasma OPN in the same population, and to assess whether OPN levels can aid in the diagnostic distinction of patients with MPM versus benign respiratory disease (BRD) and healthy subjects exposed to asbestos.
  
  
  METHODS
  The influence of preanalytic variables such as the length of storage at different temperatures and the number of thawings of samples on serum and plasma OPN measurements were evaluated. We measured OPN in 239 plasma samples from 207 asbestos-exposed subjects including 94 healthy controls and 113 subjects with BRD, and 32 patients with epithelial MPM, employing a commercially available ELISA. Serum OPN was measured in 196 of the same 239 samples from 80 healthy subjects, 92 BRD patients and 24 MPM patients.
  
  
  RESULTS
  We found that both serum and plasma OPN levels were influenced by storage at -80°C and by the number of thawings, while serum OPN was influenced also by storage at room temperature. Plasma and serum OPN levels were significantly higher (p<0.0001) in patients with epithelial MPM than in the healthy control group and the BRD group. The application of a ROC curve for plasma OPN resulted in an AUC value of 0.780 with a best cutoff of 878.65 ng/mL, with a sensitivity of 68.8% and a specificity of 84.5%. The AUC for sOPN was 0.725 with a best cutoff of 16.06 ng/mL, with a sensitivity of 62.5% and a specificity of 87.3%. Within the control group no significant correlation was observed between age, duration of asbestos exposure, pack-years in current smokers, lung function or imaging parameters and plasma or serum OPN.
  
  
  CONCLUSIONS
  These data suggest that plasma OPN and serum OPN are not influenced by confounding factors such as age, smoking habits and asbestos exposure. Plasma and serum OPN may be useful markers in the diagnosis of epithelial MPM in addition to traditional radiological exams. However, in our opinion plasma OPN is preferable to serum OPN because it is more stable and measurements of OPN in serum are less reliable.
authors.affiliation: Department of Endocrinology and Metabolism, Orthopedics and Traumatology, Occupational Medicine, University of Pisa, Pisa, Italy. a.cristaudo@med.unipi.it
authors.forename: Alfonso
authors.initials: A
authors.lastname: Cristaudo
authors.forename: Rudy
authors.initials: R
authors.lastname: Foddis
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bonotti
authors.forename: Silvia
authors.initials: S
authors.lastname: Simonini
authors.forename: Agnese
authors.initials: A
authors.lastname: Vivaldi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Guglielmi
authors.forename: Nicolino
authors.initials: N
authors.lastname: Ambrosino
authors.forename: Pier Aldo
authors.initials: PA
authors.lastname: Canessa
authors.forename: Antonio
authors.initials: A
authors.lastname: Chella
authors.forename: Marco
authors.initials: M
authors.lastname: Lucchi
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mussi
authors.forename: Luciano
authors.initials: L
authors.lastname: Mutti
mesh_terms: D000368:Aged; D001194:Asbestos / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000097:blood*; D001793:Blood Preservation / Q000379:methods; D001800:Blood Specimen Collection; D015925:Cryopreservation; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000097:blood* / Q000209:etiology; D008875:Middle Aged; D009784:Occupational Diseases / Q000097:blood / Q000209:etiology; D016273:Occupational Exposure; D053495:Osteopontin / Q000097:blood*; D010949:Plasma; D010997:Pleural Neoplasms / Q000097:blood* / Q000209:etiology; D012120:Respiration Disorders / Q000097:blood; D044967:Serum; D012907:Smoking / Q000097:blood; D013048:Specimen Handling; D013696:Temperature
chemical_list: D014408:Biomarkers, Tumor; D053495:Osteopontin; D001194:Asbestos