Potential diagnostic value of methylation profile in pleural fluid and serum from cancer patients with pleural effusion.
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.
Benlloch
Susana
S
Research Unit, Alicante University General Hospital, Alicante, Spain. benlloch_sus@gva.es
Galbis-Caravajal
Jose Marcelo
JM
Martín
Concepcion
C
Sanchez-Paya
Jose
J
Rodríguez-Paniagua
Jose Manuel
JM
Romero
Santiago
S
Mafe
Juan Jose
JJ
Massutí
Bartomeu
B
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