Utility of Promoter Hypermethylation for Differentiating Malignant and Benign Effusions in Liquid-Based Cytology Specimens

ABSTRACT

BACKGROUND: Making the cytologic differentiation between benign and malignant effusions can be difficult. Because promoter hypermethylation of tumor suppressor genes is a frequent epigenetic event in many human cancers, it could serve as a marker for the diagnosis of cancer. The aim of this study was to investigate the feasibility of detecting promoter hypermethylation as a diagnostic tool with using liquid-based cytology samples for differentiating between malignant and benign effusions. METHODS: A multiplex, nested, methylation-specific polymerase chain reaction analysis was used to examine promoter methylation of 4 genes (retinoic acid receptor-beta, [RAR-beta], adenomatous polyposis coli [APC], Twist and high in normal-1 [HIN-1]) in malignant (n = 85) and benign (n = 31) liquid-based cytology samples. RESULTS: The frequencies of hypermethylation of RAR-beta, APC, Twist and HIN-1 were significantly higher in the malignant effusions than in the benign effusions (p < 0.001 for each). On the receiver-operating characteristic analysis, the area under the curve (AUC) for APC was the greatest. The AUC for the best two-gene combination (APC/HIN-1) was not statistically different from the AUC for the best individual tumor suppressor gene (APC). CONCLUSIONS: This study suggests that promoter methylation analysis on residual liquid-based effusion samples may be a feasible approach to detect malignant effusions, and that APC is the best marker for differentiating between malignant and benign effusions.