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The Korean Journal of Pathology 2010;44(3): 315-321.
doi: https://doi.org/10.4132/KoreanJPathol.2010.44.3.315
Utility of Promoter Hypermethylation for Differentiating Malignant and Benign Effusions in Liquid-Based Cytology Specimens.
Ga Eon Kim, Jo Heon Kim, Yeong Hui Kim, Chan Choi, Ji Shin Lee
1Department of Pathology, Chonnam National University Medical School and Research Institute of Medical Sciences, Gwangju, Korea. jshinlee@hanmail.net
2Department of Pathology, Jeju National University School of Medicine, Jeju, Korea.
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.
Key Words: Liquid based cytology; Malignancy; Body fluids; Methylation; Polymerase chain reaction
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