| Purpose:To investigate the expression of caveolin-1,Dnmt1 genes in normal gastric mucosa,atypical gastric hyperplassia and gastric carcinomas,and detect methylation status of CpG island of caveolin-1 gene promoter region in gastric carcinoma and furtherly to study the correlation between caveolin-1,Dnmt1 genes expression and tumorgenesis,development and biological behaviour in gastric carcinoma.Methods:The expressions of caveolin-1,Dnmt1 proteins in 20 cases of normal gastric tissues,40 cases of atypical gastric hyperplasia,70 cases of gastric carcinoma were detected by immunohistochemistry SP method.The expression of Dnmt1mRNA in 20 cases of normal gastric tissues,40 cases of gastric hyperplasia and 60 cases of gastric carcinoma was detected by in situ hybridization(ISH).37 cases of gastric carcinoma samples and matched 7 cases of normal gastric tissues were detected by methylation specific PCR(MSP)method,meanwhile SP immunohistochemcal method and in site hybridization(ISH)were used to detect the expression of caveolin-1 protein and Dnmt1 protein,mRNA.Results:1.The positive expression of Dnmt1 preotein in normal gastric mucosa was 0%(except proliferative zones of foveolar epithelia and lymphocytes),but was 70%in gastric carcinoma.The positive rates of Dnmt1 protein was gradually increased in normal gastric mucosa,atypical gastric hyperplassia and gastric carcinomas were 0%(0/20), 35.0%(14/40)and 70.0%(49/70),and there was statistical difference among the 3 groups (χ~2=34.710,P＜0.001).The positive expression rates of Dnmt1 preotein in well, moderately,poorly differentiated adencarcinoma were 60.0%(12/20),82.4%(14/17), 67.9%(23/33),and there were no statistical difference among the 3 groups(χ~2=2.189, P＞0.05).Immunoreactivity for caveolin-1 protein was detected in in the cytoplasm of normal gastric mucosa and atypical gastric hyperplasia,but scarcely in gastric carcinomas.The positive expression rates of caveolin-1 protein in normal gastric mucosa, atypical gastric hyperplasia and gastric carcinoma were 90.0%(18/20),82.5%(33/40), 28.6%(20/70),and gradually decreased with significant statistical difference(χ~2=41.806, P＜0.001).The positive expression rates of caveolin-1 preotein in well,moderately, poorly differentiated adencarcinoma were 50.0%(10/20),41.2%(7/17)and 18.2% (6/33),and there was statistical difference among the 3 groups(χ~2=6.419,P＞0.05).2.Theχ~2 test showed that the expression of Dnmt1 protein was related to lymph node metastasis of the malignant progression of gastric carcinoma(P＜0.05),but was not correlated with patient's age,gender,invasion depths and vessel invasion(P＞0.05),and the expression of protein caveolin-1 was related to lymph node metastasis,invasion depths and vessel invasion(P＜0.05).3.Spearman rank correlation analysis indicated that the expression of Dnmt1 protein was negatively correlated with that of caveolin-1 protein(r_s=-0.929,P＜0.05).4.The positive expression of Dnmt1 mRNA was negative expression in normal gastric mucosa(except proliferative zones of foveolar epithelia).The positive expression rates of Dnmt1 mRNA in normal gastric mucosa,atypical gastric hyperplasia and gastric carcinoma were 0%(0/20),25.0%(10/40)and 63.3%(38/60)with statistical differences (χ~2=30.694,P＜0.001).The positive expression rates of caveolin-1 preotein in well, moderately,poorly differentiated adencarcinoma were 50.0%(8/16),58.8%(10/17)and 74.0%(20/27),and there was statistical difference among the 3 groups(χ~2=6.419, P＞0.05).5.Spearman rank correlation analysis indicated that the expression of Dnmt1 mRNA was positively correlated with Dnmt1 protein(r_s = 1.000,P＜0.01).6.The methylation positive rate of CpG island in caveolin-1 gene promoter region was 73.3%(22/30)in gastric carcinomas,amomg which there was 43.3%(13 cases) showed complete methylation,and 30.0%(9 cases)of merimethylation.The positive expression rates of caveolin-1 protein,Dnmt1 protein and Dnmt1 mRNA were 30.0% (9/30),63.3%(19/30)and53.3%(16/30).7.Fisher's exact ratio test demonstrated that the methylation of CpG island in caveolin-1gene promoter region was positively correlated with patient's age(P＜0.05), and not related to patient's gender,lymph node metastasis,the size of tumor,invasion depths and vessel invasion(P＞0.05).Conclusion:1.The positive expression rate of Dnmt1 protein in gastric carcinoma is remarkly higher than that in atypical gastric hyperplasia and normal gastric tissues,and the expression can reflect carcinomas' invasion potentiality,but the expression of caveolin-1 with the opposite trend.The combined examination of caveolin-1 and Dnmt1 proteins 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 increased expressions both Dnmt1 protein and mRNA indicate that the malignant transformation process and the gastric carcinomas' invasion potentiality.3.The suppressed expressions of caveolin-1 gene are related with CpG island methylation and the increased expression of Dnmt1 gene in gastric carcinoma. |
PDF Full Text Request