The Prognostic Value Of E-Cadherin In Hydatidiform Mole And The Study Of E-Cadherin Gene Promoter Hypermethylation

Objective To investigate the role of E-cadherin expression and the promoter methylation of E-cadherin gene in the malignant transformation process of hydatidiform mole. To explore the possibility of re-expression of the methylated and silenced E-cadherin gene through DNA methyltransferase inhibitor5-Aza-CdR. Methods SP immunohisto-chemistry technique was performed to search for protein expression of E-cadherin gene in the tissues of37cases of hydatidiform moles and10cases of normal chorionic villi. Methylation specific polymerase chain reaction (MSP) was used to detect methylation state of E-cadherin gene promoter in normal chorionic villi、spontaneous regressive moles、malignant moles and the human choriocarcinoma cells(JAR). The re-expression of E-cadherin mRNA was detected by RT-PCR after treatment with5-Aza-CdR. Results1. E-cadherin protein was present in100%of normal chorionic villi,90%of spontaneous regressive moles,41.8%of malignant moles.The result showed a depressing trend in the expression of E-cadherin in normal chorionic villi、spontaneous regressive moles and malignant moles, there was significant difference between each two groups (χ2=12.903,P<0.05). There was no significant difference of E-cadherin expression between normal chorionic villi and spontaneous regressive moles (P=0.540)2. In contrast, E-cadherin methylation was present in0%of normal chorionic villi,15%of spontaneous regressive moles,41.8%of malignant moles. E-cadherin methylation status showed an increasing trend (χ2=4.573,P<0.05). The levers of E-cadherin methylation in malignant moles were higer than that normal chorionic villi, there was significant difference between two groups (P<0.05). The expression of E-cadherin in DNA methylation group were lower than those of DNA non-methylation group (tau-b=0.769, P<0.05).3. E-cadherin methylation in malignant moles was associated with clinic stages (tau-b=-0.757,P<0.05).4. In JAR cell line, methylation was found in the promoter region, and the expression of E-cadherin mRNA was weak. After treatment with5-Aza-CdR, expression of E-cadherin gene was enhanced in the choriocarcinoma cell line JAR.Conclusions (1) Compared with normal chorionic villi, the expression of E-cadherin protein in normal chorionic villi、spontaneous regressive moles is decreased. Downregulation of E-cadherin expression was found to be related to CpG islands methylation status of E-cadherin. We conclude that aberrant methylation may be an important mechanism for the inactivation of E-cadherin gene, and play an important role in the malignant progression of the hydatidiform mole.(2)5-Aza-CdR could reverse the demethylation of E-cadherin gene, and recover the function of E-cadherin gene.