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Expression Of HMSH2 MRNA And Promoter Region Methylation

Posted on:2005-07-10Degree:MasterType:Thesis
Country:ChinaCandidate:G Y ZhangFull Text:PDF
GTID:2144360125457577Subject:Histology and Embryology
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Background and Objective China is the country where the rate of death and attack of esophageal cancer is the highest in the world, there is fifteen thousand new patients attacked esophageal cancer in China, which is half of the sum of world's, Lin county and his neighbor Hui county, Anyang and so on, are the region with the highest rate of death and attack of esophageal cancer not only in China but also in the world. Oncogene, anti-oncogene and DNA mismatch repair play important role in tumor's occurrence and development. Thorough research has been done in HNPCC about DNA mismatch repair gene, on the other hand, there is mutation and deletion and informal methylation in promoter region in other cancer. Mismatch repair gene is conserved gene in the course of biological evolution, and which can repair DNA mismatched base, strengthen the loyalty of DNA replication, maintain the stabilization of genome, reduce the spontaneous mutation. hMSH2 is the first separated MMR, and it's deletion, mutation and informal methylation have the consanguineous relationwith cancer's occurrence and development of HNPCC, non-small-cell lung cancer, prostate cancer, and gastric carcinoma and so on. There is no report about the detection of MMR mRNA and methylation in esophageal cancer. Expression of MMR gene, hMSH2 mRNA in esophageal cancer by used of site hybrization, and the promoter DNA methylation was detected with methylation specific PCR the first time domesticly. Connecting the expression of hMSH2 with patients' clinical information, the significance of hMSH2 in the course of occurrence and development in esophageal cancer was explored.Methods To get about 2 cm? cm? cm cancer tissues, adjacent cancer tissues, and normal esophageal tissues from fresh esophageal cancer operation sample in half an hour, for 32 esophageal cancer patients who had never received radiotherapy, chemotherapy and so on. Methylation specific PCR(MSP) was used to detect hypermethylation of hMSH2 gene in tumor tissues obtained from 32 patients with esophageal cancer. The expression of hMSH2 was examined by in situ hybridization(ISH) techniques with hMSH2 detection kit. Statistical analysis was performed used the SPSS 10.0 software package. Chi-squared and Fisher's exact were applied with an alpha value of 0.05.Results ㊣n 32 cases of esophageal cancer, the positive expression of hMSH2 mRNA is 46.88% in cancer tissue, 53.12% in paracancer tissue, 84.35% in normal tissue. There was no significant difference between cancer and paracancer tissuesP > 0.05). And there was significant difference between the above two and normal tissue(P < 0.05). (2)There was no significant correlation between the positive rate of hMSH2 mRNA and age, sex, tumor size, tumor position, pathological type, histological grade, lymphatic metastasis or infiltration deepness(P > 0.05). (3) Methylation of hMSH2 promoter in cancer foci and paracancer was found in ll/32(32.4%)and 6/32(18.8%) respectively. No methylation was found in normal mucous membrana. hMSH2 hypermethylation in cancer foci was higher than that paracancer(P < 0.05). (4) hMSH2 hypermethylation in eldly patients (^70 years) (85.7%)was higher than that younger patients ( < 70 years) (20%) . In addition, thehypermethylation of hMSH2 gene in tumor tissue from patients with I ?II grads had lower occur rate(18.2%) than that III-IV grads(70%). There was no significant correlation between the methylation of hMSH2 promoter in cancer foci and sex, tumor size, tumor position, pathological type, lymphatic metastasis or infiltration deepness(P > 0.05). (? In esophageal cancer tissues, methylation of hMSH2 promoter was detected in 2/15(13.33%) of the tumor with expression of hMSH2 mRNA , and 9/17(52.95%) of the tumor without expression of hMSH2 mRNA. The former was clear lower than the latter(P < 0.05).Conclusion (T) The deletion of hMSH2 mRNA is a early event in esophageal cancer's occurrence. (2) Methylation of hMSH2 gene in promoter region was associated with genesis and progress of esophageal cancer. (3) There is certa...
Keywords/Search Tags:sesophageal cancer, hMSH2, DNA methylation, In-site hybrization, MSP
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