| Microsatellite instability and aberrant methylation of promoter CpG islands of tumor suppressor genes belong to the key contents of tumor genetic and epigenetic mechanism, respectively. They are important mechanism for instability of chromosome and genome, the inactivation of tumor suppressor genes, and carcinogenesis of some malignancies, and they are hot spots about medical research in recent years.The First Part (one)Expression of mismatch repair genes in colorectal adenocarcinomawith microsatellite instabilityObjective In this study, we analysed the clinicopathological feature of colorectal adenocarcinoma with various status on microsatellite instability, and evaluated the feasibility for identification of these tumor using immunohisto-chemical staining for hMLH1 and hMSH2 in tumor tissues of colorectal adenocarcinoma. Materials and Methods One hundred and four tumor specimens from surgical resection of colorectal adenocarcinoma at Zhongnan hospital, Wuhan university were assayed in this study between October 2001 and June 2003, at the same time, the paired normal colonic mucosa tissues far from tumor 5 centimeters were used as control group. All subjects were the unrelated Han people in Hubei province of China, and all the samples were identified by light microscopy on haematoxylin and eosin sections. Microsatellite status on colorectal adenocarcinoma was determined by polymerase chain reaction (PCR) amplification, and then stained by silver nitrate, while immunostaining was used to examine expression of hMLHl and hMSH2. Five microsatellite sites used in this study were BAT25, BAT26, D2S123, D5S346 and D17S250. Results (1) In our study, twenty five percent of tumors showed high level microsatellite instability (MSI-H), 6.7% was low high level microsatellite instability (MSI-L), and the remainder (68.3%) was microsatellite stability (MSS). The rate of positive of microsatellite sites D2S123,BAT26, BAT25, D5S346 and D17S250 was 24.8%, 15.4%, 18.8%, 19.7% and 21.4%, respectively. Compared to the MSS/MSI-L tumors, the female patients (x2=5.05, P=0.025), non-elder patients (x2=6.81, P=0.009), tumors in proximal colon (x2=0.42, P=0.001), and poorly differentiated tumors (x2=14.01, v=2, P=0.001) were significant common among MSI-H tumors; (3) The frequency of loss of expression of hMLHl or hMSH2 was significantly higher among MSI-H tumors (26/26) when compared against the MSS/MSI-L tumors (7/78, x2=74.59, P<0.0001), there was a highly significant negative correlation between MSI-H tumors and loss of expression of hMLHl or hMSH2 (r=-0.847, P<0.0001). Conclusions (1) There exists be significant difference about the clinicopathological features of colorectal adenocarcinoma among various MSI status, and there are much more female patients, non-elder patients, and poorly differentiated tumors among MSI-H tumors, and most tumors are in the proximal colon; (2) The rate of expression of hMLHl is significant higher among MSS/MSI-L tumors, and there is a highly significant negative correlation between MSI-H tumors and expression of hMLHl and hMSH2, immunohistochemical staining for hMLHl and hMSH2 represents an inexpensive and accurate means of identifying such microsatellite status of colorectal adenocarcinoma.The First Part (Two)Genetic polymorphisms of xenobiotica metabolizing enzymes incolorectal adenocarcinoma with microsatellite instabilityObjective In this study, we analysed genetic polymorphisms of xenobiotica metabolizing enzymes in colorectal adenocarcinoma with various microsatellite status, and the interaction between environment and hereditary factors on colorectal carcinogenesis and the inherit susceptibility of colorectal adenocarcinoma. Materials and Methods The patients were the same as the first chapter, 101 subjects were unrelated healthy Han people in Hubei province of China who received a routine health examination at our hospital as the controls, 70 were male and 31 were female, the mean age was 55.8. Genetic polymorphisms of the GSTM1, GSTT1 genes were detected by multiple PCR, NAT1 gene... |
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