title: Hyaluronan and N-ERC/mesothelin as key biomarkers in a specific two-step model to predict pleural malignant mesothelioma.
abstract: OBJECTIVE
  Diagnosis of malignant mesothelioma is challenging. The first available diagnostic material is often an effusion and biochemical analysis of soluble markers may provide additional diagnostic information. This study aimed to establish a predictive model using biomarkers from pleural effusions, to allow early and accurate diagnosis.
  
  
  METHODS
  Effusions were collected prospectively from 190 consecutive patients at a regional referral centre. Hyaluronan, N-ERC/mesothelin, C-ERC/mesothelin, osteopontin, syndecan-1, syndecan-2, and thioredoxin were measured using ELISA and HPLC. A predictive model was generated and validated using a second prospective set of 375 effusions collected consecutively at a different referral centre.
  
  
  RESULTS
  Biochemical markers significantly associated with mesothelioma were hyaluronan (odds ratio, 95% CI: 8.82, 4.82-20.39), N-ERC/mesothelin (4.81, 3.19-7.93), CERC/mesothelin (3.58, 2.43-5.59) and syndecan-1 (1.34, 1.03-1.77). A two-step model using hyaluronan and N-ERC/mesothelin, and combining a threshold decision rule with logistic regression, yielded good discrimination with an area under the ROC curve of 0.99 (95% CI: 0.97-1.00) in the model generation dataset and 0.83 (0.74-0.91) in the validation dataset, respectively.
  
  
  CONCLUSIONS
  A two-step model using hyaluronan and N-ERC/mesothelin predicts mesothelioma with high specificity. This method can be performed on the first available effusion and could be a useful adjunct to the morphological diagnosis of mesothelioma.
authors.affiliation: Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Filip
authors.initials: F
authors.lastname: Mundt
authors.forename: Gustav
authors.initials: G
authors.lastname: Nilsonne
authors.forename: Sertaç
authors.initials: S
authors.lastname: Arslan
authors.forename: Karola
authors.initials: K
authors.lastname: Csürös
authors.forename: Gunnar
authors.initials: G
authors.lastname: Hillerdal
authors.forename: Huseyin
authors.initials: H
authors.lastname: Yildirim
authors.forename: Muzaffer
authors.initials: M
authors.lastname: Metintas
authors.forename: Katalin
authors.initials: K
authors.lastname: Dobra
authors.forename: Anders
authors.initials: A
authors.lastname: Hjerpe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis*; D006801:Humans; D006820:Hyaluronic Acid / Q000032:analysis*; D016015:Logistic Models; D008297:Male; D000090204:Mesothelin; D008654:Mesothelioma / Q000175:diagnosis* / Q000378:metabolism; D008875:Middle Aged; D008954:Models, Biological; D053495:Osteopontin / Q000032:analysis; D010996:Pleural Effusion / Q000378:metabolism; D016066:Pleural Effusion, Malignant / Q000175:diagnosis* / Q000378:metabolism; D011446:Prospective Studies; D012372:ROC Curve; D053668:Syndecan-1 / Q000032:analysis; D053669:Syndecan-2 / Q000032:analysis; D013879:Thioredoxins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D053668:Syndecan-1; D053495:Osteopontin; D053669:Syndecan-2; D013879:Thioredoxins; D006820:Hyaluronic Acid; D000090204:Mesothelin