Expression Of Ezrin Gene And Detection Of Its CpG Island Methylation In Gastric Carcinomas

Purpose To investigate the expression of Ezrin gene in normal gastric mucosa, atypical gastric hyperplassia and gastric carcinoma, and detect methylation status of CpG island in Ezrin gene promoter region in gastric carcinoma and furtherly to study the correlation between Ezrin gene expression and tumorgenesis, development and biological behaviour in gastric carcinoma.Methods The expressions of Ezrin, c-Met and ICAM-1 protein in 15 cases of normal gastric tissues, 50 cases of gastric hyperplasia, 75 cases of gastric carcinoma were detected by immunohistochemistry SP method and tissue microarray technique. The expression of Ezrin mRNA in 15 cases of normal gastric tissues, 40 cases of gastric hyperplasia, and 60 cases of gastric carcinoma was detected by in situ hybridization and tissue microarray technique. 12 gastric carcinoma samples and matched normal gastric tissues were detected by methylation specific PCR (MSP) method.Results:1.The positive expression rates of Ezrin and c-Met proteins in normal gastric mucosa, gastric hyperplasia and gastric carcinoma were 100%( 15/15 ), 84. 0% (42/50), 41. 3% (31/75) and 100%(15/15), 58. 0% (29/50), 38. 7% (29/75) resepectively.The positive rates of two proteins were gradually decreased, and there were statistical difference among the 3 groups (X~2=33.319,P<0.001;X~2=19.913,P<0.001). The positive expression rates of Ezrin and c-Met proteins in well, moderately, poorly differentiated adencarcinoma and mucinous adencarcinoma were 53.3% (8/15) ,50. 0% (12/24), 33. 3%(7/21), 26.796(4/15), and 60. 0%(9/15), 45. 8%(11/24), 33.3% (7/21) , 13. 3%(2/15) resepectively, and there were no statistical difference among the 4 groups (X~2=3.519, P>0.05; X~2=7.709, P>0.05). The positive expression rates of ICAM-1 protein in normal gastric mucosa, gastric hyperplasia and gastric carcinoma were gradually increased with significant statistical difference (X~2 =16.409,P<0.001), and in well , moderately , poorly differentiated adencarcinoma and mucinous adencarcinoma were 60.0% (9/15), 45.8% (11/24), 33.3% (7/21) and 13. 3% (2/15) resepectively with negative statistical difference (X~2=1.445, P>0.05).2.The expressions of Ezrin, c-Met and ICAM-1 proteins were related to the malignant progression of gastric carcinoma, tumor diameter and lymph node metastasis (P<0.05), but they were not correlated with patient's age, gender and vessel invasion (P>0.05).3.The expression of Ezrin protein was positively correlated with that of c-Met protein (r=0.880,P<0.05), but negatively correlated with that of ICAM-1 protein (r=-0.735,P<0.05). The expression of c-Met protein was not correlated with that of ICAM-1 protein.4.The positive expression rates of Ezrin mRNA in normal gastric mucosa, gastric hyperplasia and gastric carcinoma were gradually decreased, and there were statistical difference among the 3 groups (X~2=23.599, P<0.001). The positive expression rates of Ezrin mRNA in well, moderately, poorly differentiated adencarcinoma and mucinous adencarcinoma were 50.0% (6/12) , 40. 0%(8/20), 26. 7% (4/15) and 23.1% (3/13) resepectively, and statistical differences among the 4 groups were not significant (X~2=2.677, P>0.05). The expression of Ezrin mRNA was related to the malignant progression of gastric carcinoma, tumor diameter and lymph node metastasis (P<0.05), but was not correlated with patient's age, gender and vessel invasion (P>0.05).5.The expression of Ezrin mRNA was positively correlated with Ezrin protein (r=0.990, P<0.01).6.Methylation of CpG island in Ezrin gene promoter region was found in 4 cases gastric carcinoma among all 12 cases. The positive rate was 33.3%.Conclusion1. The positive rate of Ezrin expression in gastric carcinoma is remarkly lower than that in normal gastric tissues and this low-expression can reflect carcinomas' invasion potentiality. The combined examinations of Ezrin, c-Met and ICAM-1 expression are helpful for the prediction of the invasion and metastasis status in gastric carcinoma and can make as markers for elvalating the biological behavior of gastric carcinoma.2. The identical decreased expressions both Ezrin protein and mRNA indicate that the expression of Ezrin gene is inhibited at the level of transcription or before.3. The suppressed expressions of Ezrin gene are related with CpG island methylation in promoter region in gastric carcinoma.