Microsatellite Alterations and Cell-Free DNA Analysis: Could They Increase the Cytology Sensitivity in the Diagnosis of Malignant Pleural Effusion?

Abstract

The exact diagnosis of malignant pleural effusions (PE) is difficult and often requires combined procedures, because the cytological examination of pleural fluid does not detect tumoral cells in 40% of malignant effusion cases. The aim of this study was to analyze microsatellite alterations (MA) in malignant PE and to determine their diagnostic value as an additional test to cytological examination. The increase in cell-free DNA levels was also evaluated as a signal of probable malignancy. A total of 84 patients with PE were enrolled and underwent PE and whole blood and exhaled breath condensate analyses. Free DNA was measured by spectrophotometer analyses. DNA was extracted from all samples and analyzed for MA, using the microsatellite markers at chromosomes 3p, 12p, 5q, and 17p. The microsatellite analysis of PE exhibited a higher percentage of alterations in malignant PE than in benign PE. In addition to this, cell-free DNA in PE was seen to be significantly more elevated in malignant than in benign PE. The sensitivity of the sole cytology increased considerably when patients showed at least one MA or DNA>4 ng/μL in the PE. In conclusion, it was seen that the combination of the cytological examination with microsatellite analyses and cell-free DNA in pleural fluid could increase the sensitivity of the diagnosis in patients with PE who have a suspected malignancy, obviating the need for other invasive diagnostic procedures.