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

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±è°¡¾ð ( Kim Ga-Eon ) 
Àü³²´ëÇб³ ÀÇ°ú´ëÇÐ º´¸®Çб³½Ç

±èÁ¶Çå ( Kim Jo-Heon ) 
Á¦ÁÖ´ëÇб³ ÀÇÇÐÀü¹®´ëÇпø º´¸®Çб³½Ç
±è¿µÈñ ( Kim Yeong-Hui ) 
Àü³²´ëÇб³ ÀÇ°ú´ëÇÐ º´¸®Çб³½Ç
ÃÖÂù ( Choi Chan ) 
Àü³²´ëÇб³ ÀÇ°ú´ëÇÐ º´¸®Çб³½Ç
ÀÌÁö½Å ( Lee Ji-Shin ) 
Àü³²´ëÇб³ ÀÇ°ú´ëÇÐ º´¸®Çб³½Ç

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-¥â, [RAR-¥â], 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-¥â, 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.

Å°¿öµå

Liquid based cytology;Malignancy;Body fluids;Methylation;Polymerase chain reaction

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