Epigenetic Changes in Tumor Suppressor Genes, P15, P16, APC-3 and E-cadherin in Body Fluid

Abstract

The inactivation of tumor suppressor genes by promoter methylation plays an important role in the development of cancers; it can also be used as a marker to distinguish cancerous cells from non-cancer cells. In this study, we investigated the aberrant methylation profile of the tumor suppressor genes P15, P16, APC and E-cadherin in the cells of body fluid. A methylation-specific polymerase chain reaction was performed in 31 cases of malignant effusion and 39 cases of non-malignant effusion. Aberrant promoter methylation of P15, P16, APC and E-cadherin genes was seen in 0%, 25.8%, 35.5% and 6.5% of malignant effusion cases, respectively, whereas the frequencies were 0%, 2.6%, 2.6% and 0%, respectively, for negative control effusion. There were statistically significant differences in the aberrant methylation of P16 (p = 0.008) and APC (p = 0.018) genes between cases of malignant effusion and controls. Methylation of one of three genes (P16, E-cadherin, APC) was found in 14 out of 31 (45.2%) cases of malignant effusion, and in two out of 39 (5.1%) cases of non-malignant effusion (p = 0.000004). Concurrent methylation was found in nine out of 31 (29%) cases of malignant effusion, but in no non-malignant effusion sample. From these results, we suggest that methylation-specific polymerase chain reaction to analyze the promoters of tumor suppressor genes can distinguish between malignant effusion and benign effusion, and may help cytologists to make more accurate diagnoses.