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Susana Benlloch is the recipient of a research contract from the Spanish Ministry of Health.
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Original Article
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Potential diagnostic value of methylation profile in pleural fluid and serum from cancer patients with pleural effusion†
Article first published online: 18 SEP 2006
DOI: 10.1002/cncr.22190
Copyright © 2006 American Cancer Society
Additional Information
How to Cite
Benlloch, S., Galbis-Caravajal, J. M., Martín, C., Sanchez-Paya, J., Rodríguez-Paniagua, J. M., Romero, S., Mafe, J. J. and Massutí, B. (2006), Potential diagnostic value of methylation profile in pleural fluid and serum from cancer patients with pleural effusion. Cancer, 107: 1859–1865. doi: 10.1002/cncr.22190
- †
Presented in part at the International Association for the Study of Lung Cancer 11th World Conference on Lung Cancer, Barcelona, Spain, July 3–6, 2005.
Publication History
- Issue published online: 3 OCT 2006
- Article first published online: 18 SEP 2006
- Manuscript Accepted: 6 JUL 2006
- Manuscript Revised: 14 JUN 2006
- Manuscript Received: 10 FEB 2006
Funded by
- Spanish Ministry of Health. Grant Number: (FIS 01/3080)
- Spanish Society of Medical Oncology
- Abstract
- Article
- References
- Cited By
Keywords:
- carcinoma;
- DNA methylation;
- diagnosis;
- pleural fluid;
- tumor marker;
- polymerase chain reaction
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 β (RARβ), 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. Cancer 2006. © 2006 American Cancer Society.