Study On Relationship Between Expression Of E-cadherin And CpG Island Hypermethylation Around Promoter Region Of Its Gene In Ovarian Cancer

Objective: To study the expression of E-cadherin and DNMT1 and CpG islands methylation status of E-cadherin's promoter region in normal ovaries, benign ovarian tumours and epithelial ovarian carcinomas, as well as the correlations with several clinicopathologic characteristics, and to provide the theoretical basis and strategies for clinical biotherapy and preventions.Method: The protein levels of E-cad and DNMT1 were detected by animmunohistochemical analysis in formalin-fixed, paraffin-embedded samples of 18 normal ovaries, 30 benign epithelial ovarian tumours and 40 epithelial ovarian carcinomas, using the antibody specific against these two proteins respectively. MSP was to determine the methylation status of CpG island in promoter region of E-cad.Results:1 E-cad expression was absent in normal ovarian surface epithelium;the expression of E-cad in epithelia carcinomas was significantly lower than its in benign ovarian tumours(t =4.576, P<0.05). Higher expression in mucinous cancer than in other type of ovarian cancers;A reverse correlation were found in the expression of E-cad and the histological grade(r=-0.551, P<0.05);As to clinical stage, E-cad expression was significantly higher in I -II stage than in III ~ IV stage (t= 2.151, P<0.05);The expression of E-cad in patients of ascites without tumor cells was significantly higher than its in the patients of ascites with tumor cells(t=2.246, P<0.05).2 The frequency of CpG islands methylation status of E-cad promoter region in epithelial ovarian carcinomas was higher than that in benign ovarian tumors andnormal ovaries( x~2=6.958, P<0.05);The difference of the frequency of CpG islands methylation status of E-cad promoter region between benign ovarian tumors and normal ovaries was statistically insignificant;There was no difference for CpG islands methylation status of E-cad promoter region in different type and tumor cells in ascites;Significant difference in different grades and stage, lower in G1~G2 and early stage than in G3 and advanced stage.3n DNMT1 was expressed in normal ovaries, benign ovarian tumours and epithelial ovarian carcinomas. The expression of DNMT1 in epithelial ovarian carcinomas was significantly higher than its in benign ovarian tumors and normal ovaries(F= 11.581, PO.05). The difference of DNMT1 level between benign ovarian tumors and normal ovaries was statistically insignificant(/=1.393, P>0.05). There was no difference for DNMT1 protein expression in different type;A positive correlation were found in the expression of DNMT1 and the histological grade(r=0.479, PO.05);As to clinical stage, DNMT1 expression was significantly lower in I -— II stage than in III—IV stage(/=2.227, PO.05);The expression of DNMT1 in patients of ascites without tumor cells were significantly lower than its in the patients of ascites with tumor cells(/=3.595, PO.05).4n The expression of E-cad which were positive for the CpG islands methylation in E-cad gene promoter region was significantly less than that in the negative group(/ =3.463, PO.05);The expression of E-cad was significantly correlated with CpG islands methylation status of E-cad promoter region(r=0.490, PO.05). In epithelial ovarian carcinomas, the expression of E-cad was insignificantly correlated with that of DNMTl(r = 0.162;P>0.05). The expression of DNMT1 was insignificantly correlated with CpG islands methylation status of E-cad promoter region(r=0.134,P>0.05).5> The expression of E-cad and DNMTl appeared not to be associated significantly with the patients' survival time, as well as the frequency of CpG islands methylation status of E-cad promoter. region(Log-rank test 1.39 ^ 0.2 > 1.71 respectively, P>0.5).Conclusion: In epithelial ovarian carcinomas, the expression of E-cad andDNMTl was correlated with tumour differentiation and clinical stage. E-cad was higher expressed in highly differentiation and early stage tumors, but DNMTl was lower in those cancer. E-cad and DNMTl may play an important role in development of malignancies. Downregulation of E-cad expression was found to be related to CpG islands methylation status of E-cad promoter region. We conclude that aberrant methylation may be an important mechanism for the inactivation of this gene, then disrupt cell-cell adhesion in carcinoma cell and lead to a more invasive phenotype.