Diagnostic value of the FHIT and p16 mRNA loss and the K-ras gene mutation in pleural fluids for malignant pleural effusion.

Inactivation of the tumor suppressor genes and activation of oncogenes are involved in the development of cancer. The aim of this study was to evaluate the diagnostic value of the fragile histidine triad (FHIT) and p16 mRNA loss and the K-ras gene mutation in distinguishing malignant from benign pleural effusion. A total of 50 patients with malignant pleural effusion and 30 patients with benign pleural effusion were enrolled in this study. All pleural fluid specimens were evaluated in parallel by cytology, reverse transcriptase-PCR for the loss of FHIT and p16 mRNA, and PCR-SSCP (single-stranded conformation polymorphism) for the mutation of K-ras gene. The detection rates of FHIT and p16 mRNA loss were significantly higher in malignant than in benign pleural effusion (P < 0.001 and P = 0.001). The K-ras mutations were more frequent in malignant than benign pleural effusion (P = 0.006). The sensitivity and specificity were 58% and 93% for FHIT loss, 48% and 90% for p16 loss, and 44% and 87% for the K-ras mutation, respectively. In combined evaluation with both FHIT and p16 loss, the sensitivity was 68%, and specificity was 90%. The combination of the three molecular markers reached 74% sensitivity, whereas the combined use of the cytology and the three markers increased the diagnostic yield of the former by 38%. More than one third of cytology negative malignant pleural effusion could be identified by at least one of the three markers. These results suggest that the detection of FHIT and p16 mRNA loss and the k-ras gene mutation in pleural fluid could be helpful adjunct to cytology in the diagnosis of malignant pleural effusion.