| Colorectal carcinoma(CRC) is one of the most common malignant tumors in digestive tracts, and its mechanism is rather complicated. Previous studies have shown the association between colorectal carcinogenesis and the mutation of K-ras and c-myc oncogenes,inactivation of tumor suppressor genes such as P53,APC,DCC,MCC,P53 etc. However, more recent studies have revealed that none of these genes is linked to carcinogenesis in hereditory non-polyposis colorectal cancer(HNPCC). The HNPCC carcinogenesis has been found to be related to mutation in mismatch repair genes and microsatellite instability(MSI). The changes have been soon found in sporadic CRCs, gastric carcinomas, and breast carcinomas. These studies suggested that mutation in mismatch repair genes and microsatellite instability may be a new mechanism in tumorigenesis. To our knowledge,the investigations on expression of mismatch repair gene and MSI in major precancerous lesion(colorectal adenoma)were few, and the relationship between the expression of mismatch repair gene and MSI with the apoptosis and proliferation in colorectal adenoma and malignant change type in adenomas remains unclear.Therefore,in the present study,we investigated the expression of mismatch repair gene hMLH1 and hMSH2,PCNA and Ki-67,apoptosis controlling gene Bcl-2 and Bax by immunohistochemistry,and examined the status of apoptosis by TUNEL,and examined MSI at six microsatellite loci (D18S34,D17S799, D5S409, TCF-2, Rb and P53) using PCR-SSLP in colorectal adenoma and malignant change type in adenomas . Meanwhile, in order to explore the role of induce of hMLH1,hMSH2 and MSI in carcinogenesis and progression of CRC,and their influences on proliferation and apoptosis,to explore the relationships between proliferation,apoptosis and MSI in colorectal adenoma and malignant change type in adenomas,in this study, we attempt to provide useful approaches to study CRC carcinogenesis. The main results are as follows:1.The expressions of mismatch repair gene hMLH1 and hMSH2 were detected in 63 cases of colorectal adenomas,20 cases of malignant change type in adenomas, 20cases of CRC and 11 cases of normal mucosa by immunohistochemistry,the results showed thepositive rate of hMLH1 and hMSH2 in colorectal adenomas,malignant change type in adenomas and CRCs were significantly lower than that in normal mucosa(p<0.01).With increasing dysplasia in adenomas, the expression rate of hMLH1 and hMSH2 protein decreased gradually, It indicated that the mismatch repair genes mutation and abnormal function of DNA mismatch repair maybe participate in carcinogenesis of CRCs. It is may be a early event in carcinogenesis of CRCs. Meanwhile, the most tumors with loss of hMLH1 and hMSH2 protein expression were located in right-side colon. It supported that its occurrence mechanism may be the difference between right-side colorectal carcinoma and left-sided colorectal tumor.2.The PCNA LI of tumors with overexpression hMSH2 were significant higher than that of tumors with negative hMSH2 in colorectal adenomas, malignant change type in adenomas and CRCs(p<0.05). PCNA LI of tumors with overexpression hMSH2 were significant higher than that of tumors with negative hMSH2 in adenomas with grade â…¡,â…¢ dysplasia(p<0.05).The change of PCNA and ki-67 LI in in colorectal adenomas, malignant change type in adenomas and CRCs were not association with the expression of hMLH1. It suggested that the reduction of proliferating activities in colorectal neoplasms may be related to mutation and defect of mismatch repair gene. 3.The AI value of clolorectal adenomas and CRCs with overexpressions hMLH1 were significant lower than that of tumors with negative hMLH1(p<0.01),the same status was among three groups in grade â… ,â…¡,â…¢ dysplasia of colorectal adenomas(p<0.05).Only the AI value of adenomas with overexpressions hMSH2 were significant lower than that of tumors with negative hMSH2,the same status was in grade â… ,â…¡dysplasia of colorectal adenomas(p<0.05). The protein exp... |
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