title: Serum mesothelin for diagnosing malignant pleural mesothelioma: an individual patient data meta-analysis.
abstract: OBJECTIVE
  Mesothelin is currently considered the best available serum biomarker of malignant pleural mesothelioma. To examine the diagnostic accuracy and use of serum mesothelin in early diagnosis, we performed an individual patient data (IPD) meta-analysis.
  
  
  METHODS
  The literature search identified 16 diagnostic studies of serum mesothelin, measured with the Mesomark enzyme-linked immunosorbent assay. IPD of 4,491 individuals were collected, including several control groups and 1,026 patients with malignant pleural mesothelioma. Mesothelin levels were standardized for between-study differences and age, after which the diagnostic accuracy and the factors affecting it were examined with receiver operating characteristic (ROC) regression analysis.
  
  
  RESULTS
  At a common diagnostic threshold of 2.00 nmol/L, the sensitivities and specificities of mesothelin in the different studies ranged widely from 19% to 68% and 88% to 100%, respectively. This heterogeneity can be explained by differences in study population, because type of control group, mesothelioma stage, and histologic subtype significantly affected the diagnostic accuracy. The use of mesothelin in early diagnosis was evaluated by differentiating 217 patients with stage I or II epithelioid and biphasic mesothelioma from 1,612 symptomatic or high-risk controls. The resulting area under the ROC curve was 0.77 (95% CI, 0.73 to 0.81). At 95% specificity, mesothelin displayed a sensitivity of 32% (95% CI, 26% to 40%).
  
  
  CONCLUSIONS
  In patients suspected of having mesothelioma, a positive blood test for mesothelin at a high-specificity threshold is a strong incentive to urge further diagnostic steps. However, the poor sensitivity of mesothelin clearly limits its added value to early diagnosis and emphasizes the need for further biomarker research.
authors.affiliation: Ghent University Hospital, Ghent, Belgium. kevin.hollevoet@nih.gov
authors.forename: Kevin
authors.initials: K
authors.lastname: Hollevoet
authors.forename: Johannes B
authors.initials: JB
authors.lastname: Reitsma
authors.forename: Jenette
authors.initials: J
authors.lastname: Creaney
authors.forename: Bogdan D
authors.initials: BD
authors.lastname: Grigoriu
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Robinson
authors.forename: Arnaud
authors.initials: A
authors.lastname: Scherpereel
authors.forename: Alfonso
authors.initials: A
authors.lastname: Cristaudo
authors.forename: Harvey I
authors.initials: HI
authors.lastname: Pass
authors.forename: Kristiaan
authors.initials: K
authors.lastname: Nackaerts
authors.forename: José A
authors.initials: JA
authors.lastname: Rodríguez Portal
authors.forename: Joachim
authors.initials: J
authors.lastname: Schneider
authors.forename: Thomas
authors.initials: T
authors.lastname: Muley
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Serio
authors.forename: Paul
authors.initials: P
authors.lastname: Baas
authors.forename: Marco
authors.initials: M
authors.lastname: Tomasetti
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Rai
authors.forename: Jan P
authors.initials: JP
authors.lastname: van Meerbeeck
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D055088:Early Detection of Cancer; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood*; D006801:Humans; D008297:Male; D000090204:Mesothelin; D008654:Mesothelioma / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D012044:Regression Analysis
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D000090204:Mesothelin