title: Serum concentration of integrin-linked kinase in malignant pleural mesothelioma and after asbestos exposure.
abstract: OBJECTIVE
  Integrin-linked kinase (ILK) is an intracellular protein implicated in chronic inflammation and neoplastic transformation. In a recently accomplished pilot study, we showed that ILK can be detected in the serum of patients with benign and malignant chest diseases, including malignant pleural mesothelioma (MPM). Interestingly, average serum ILK concentrations were 10 times higher in MPM patients when compared with the rest of the study population, and a diagnostic test solely based on serum ILK concentration could discriminate between MPM and non-MPM with considerable accuracy. This study aimed to investigate whether serum ILK concentration could also be used to discriminate between MPM and asbestos exposure only.
  
  
  METHODS
  Using a self-developed sandwich enzyme-linked immunosorbent assay, we measured serum ILK concentrations in 101 MPM patients, and 96 asbestos-exposed, but healthy insulation workers. Seventy-three MPM patients had an epitheloid subtype (72.3%), and 42 had a Stage I or II disease (41.6%).
  
  
  RESULTS
  When compared with asbestos-exposed individuals, MPM patients of all clinical stages had significantly higher (mean ± standard deviation, median) serum ILK concentrations (10.7 ± 13.6, median 7 ng/ml vs 3.1 ± 4.6, median 1.4 ng/ml; P < 0.001). Among MPM patients, the serum ILK concentration was significantly higher at advanced disease stages III + IV than at early stages I + II (13.7 ± 15.9, median 8.5 ng/ml vs 6.7 ± 7.8, median 3.5 ng/ml; P = 0.02). Using serum ILK to discriminate between MPM patients and asbestos-exposed individuals yielded an area under the curve of 0.69 (95% confidence interval 0.63-0.76). The corresponding sensitivity and specificity for a cut-off of 4.49 ng/ml ILK are 61.4 and 80.2%, respectively.
  
  
  CONCLUSIONS
  These data show significant differences between MPM patients and asbestos-exposed but healthy individuals concerning their serum ILK concentration. Furthermore, since ILK levels are increased in advanced MPM stages in comparison with early MPM stages, we suggest evaluating its potential use as a marker of disease progression in MPM.
authors.affiliation: Division of Thoracic Surgery, Otto Wagner Hospital, Vienna, Austria. s.watzka@utanet.at
authors.forename: Stefan B
authors.initials: SB
authors.lastname: Watzka
authors.forename: Florian
authors.initials: F
authors.lastname: Posch
authors.forename: Harvey I
authors.initials: HI
authors.lastname: Pass
authors.forename: Raja M
authors.initials: RM
authors.lastname: Flores
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Hannigan
authors.forename: David
authors.initials: D
authors.lastname: Bernhard
authors.forename: Michael
authors.initials: M
authors.lastname: Weber
authors.forename: Michael R
authors.initials: MR
authors.lastname: Mueller
mesh_terms: D000368:Aged; D000395:Air Pollutants, Occupational / Q000032:analysis / Q000097:blood* / Q000506:poisoning; D000704:Analysis of Variance; D001194:Asbestos / Q000506:poisoning*; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000097:blood / Q000201:enzymology* / Q000209:etiology; D008875:Middle Aged; D016273:Occupational Exposure / Q000032:analysis*; D010997:Pleural Neoplasms / Q000097:blood / Q000201:enzymology* / Q000209:etiology; D017346:Protein Serine-Threonine Kinases / Q000097:blood*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D000099200:Scaffold Protein ILK
chemical_list: D000395:Air Pollutants, Occupational; D001194:Asbestos; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK