[Studies of promoter methylation status and protein expression of E-cadherin gene in associated progression stages of gastric cancer].
Gastric cancer, like all cancers, is considered to result in part from the accumulation of multiple genetic alterations leading to oncogene overexpression and tumour suppressor loss. More recently, the role of epigenetic change as a distinct and crucial mechanism to silence a variety of methylated tissue-specific and imprinted genes has emerged in many cancer types. The study of DNA methylation changes in gastric cancer has now provided additional clues into the pathogenesis of the disease. E-cadherin as a metastases suppressor is mutationally inactivated in both familial and sporadic forms of gastric cancers. Evidence now suggests that the transcriptional silencing of E-cadherin gene by promotor methylation plays a crucial role in the development and progression of gastric malignancies. In order to further analyze the role of E-cadherin gene promotor methylation in gastric carcinogenesis and progression, we performed the studies of promoter methylation status and protein expression of E-cadherin gene in associated progression stages of gastric cancer. DNA were extracted from the paraffin embedded gastric specimens of dysplasia(23 cases), early cancer (20 cases) and advanced cancer (20 cases). Methylation specific PCR and immunohistochemistry were used to analyze the promoter methylation status and the protein expression level of E-cadherin gene. Our results showed that E-cadherin promoter methylation occurred in all stages of gastric precancerous lesion and carcinogenesis, which suggests E-cadherin promotor methylation is an important event during gastric carcinogenesis and progression. The positive rate of E-cadherin promotor methylation in dysplasia, early gastric cancer and advanced gastric cancer was 78.3%, 80% and 90% respectively. There were significant differences between experimental groups and control group(30%), P < 0.05, but no significant differences among experimental groups, P > 0.05. All of advanced gastric cancer examined were completely E-cadherin protein-negative by immunohistochemistry. Fourteen of 20 early gastric cancer were E-cadherin-negative. And 23 dysplasia were all E-cadherin-positive. Thirty-one of 34(91%) of the E-cadherin-negative tumours had promotor methylation. This result indicated the downregulation expression of E-cadherin was associated with promotor methylation in early and advanced gastric cancer (P < 0.01).
Zheng
Zhi-Hong
ZH
Department of Genetics, China Medical University, Shenyang 110001, China.
Sun
Xiu-Ju
XJ
Ma
Ming-Chao
MC
Hao
Dong-Mei
DM
Liu
Yan-Hou
YH
Sun
Kai-Lai
KL
D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D015820:Cadherins; D004273:DNA, Neoplasm