title: Potential diagnostic value of methylation profile in pleural fluid and serum from cancer patients with pleural effusion.
abstract: BACKGROUND
  The objective of this study was to investigate the diagnostic value of methylation profiles for discrimination between malignant and benign pleural effusions. A secondary objective was to examine the concordance of methylation in samples of serum and pleural fluid.
  
  
  METHODS
  The authors used methylation-specific polymerase chain reaction (MSP) analysis to examine the promoter methylation status of 4 genes in patients with pleural effusion: death-associated protein kinase (DAPK), Ras association domain family 1A (RASSF1A), retinoic acid receptor beta (RARbeta), and p16/INK4a. Pleural effusions were collected from 87 patients who had their diagnoses confirmed on cytologic and/or histologic examinations and clinical evolution. Pleural effusions were classified as malignant (n = 53 patients) or benign (n = 34 patients).
  
  
  RESULTS
  Methylation was detected in serum from 45.3% of patients with malignant pleural effusions and from 0% of patients with benign pleural effusions, and it was detected in pleural fluid samples from 58.5% of patients with malignant pleural effusions and from 0% of patients with benign pleural effusions (P = .001). The sensitivity of MSP was greater than that of cytologic examination alone (39.1%; P = .001). When MSP was used together with cytologic examination, sensitivity increased to 69.8% (P = .001).
  
  
  CONCLUSIONS
  Cell-free methylated DNA in pleural fluid can be detected in patients with neoplastic malignancy in a single extraction by thoracocentesis. Adequate management of the extracted pleural fluid can provide a rapid and reliable diagnosis in patients with pleural effusions who have suspected malignancy. MSP, used together with cytologic examination, may obviate the need for other invasive diagnostic tests.
authors.affiliation: Research Unit, Alicante University General Hospital, Alicante, Spain. benlloch_sus@gva.es
authors.forename: Susana
authors.initials: S
authors.lastname: Benlloch
authors.forename: Jose Marcelo
authors.initials: JM
authors.lastname: Galbis-Caravajal
authors.forename: Concepcion
authors.initials: C
authors.lastname: Martín
authors.forename: Jose
authors.initials: J
authors.lastname: Sanchez-Paya
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Rodríguez-Paniagua
authors.forename: Santiago
authors.initials: S
authors.lastname: Romero
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Mafe
authors.forename: Bartomeu
authors.initials: B
authors.lastname: Massutí
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D009369:Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D010996:Pleural Effusion / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D016066:Pleural Effusion, Malignant / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity