| Recent researches show that there is another major kind of gene system in the genes involved in oncogenesis, besides oncogenes, tumor suppressor genes, apoptosis genes and anti-apoptosis genes, which is known as mismatch repair (MMR) genes system. The instability of genome which results from defect of MMR genes is thought as a new oncogenesis way. The symbol of genome instability is microsatellite instability (MSI) and loss of heterozygosity (LOH). The hMLHl gene is one essential member in the MMR gene system that at least contains six genes. The role of MSI and LOH is not very clear in the oncogenesis and process of esophagus squamous cell carcinoma, as well as of MMR genes and genome instability. In this study, the microsatellite alteration and protein expression of hMLHl gene were inspected and analyzed to help clarify them.Material and Methods:40 esophagus squamous cell carcinoma samples, relevant 40 normal tissue samples and 26 dysplasia tissue samples were collected. By polymerase chain reaction (PCR) - denaturing polyacrylamide gel electrophoresis - silver staining technique, 3 microsatellite loci (D3S1561, D3S1298, D3S1448) in the site where hMLHl gene locates were checked, to analyze the status of MSI and LOH in dysplasia and tumor tissue; immunohistochemistry (IHC) staining technique was also used in this study to show the expression status of hMLHl protein in the three different kind of tissue. Then the data from the study was analyzed by chi-square test, Fisher's exact probabilities test and t-test through SPSS statistical package program.Results:1. Status of MSIIn dysplasia tissue, the positive rate of MSI in D3S1561,D3S1298,D3S1448 was 38%, 30% and 19% respectively, there were no significant differences in three loci(p>0.05). The total positive rate is 65%; in tumor tissue, the positive rate in these loci was 17.5%, 10% and 10%, there were no significant differences, either (p>0.05). The total positive rate is 30%, which was lower than the total positive rate in dysplasia tissue significantly (p<0.05). There was correlation between MSI of dysplasia tissue and that of tumor tissue (p<0.05).2. Status of LOHIn dysplasia tissue, the positive rate of LOH in D3S1561,D3S1298,D3S1448 was 0%, 0% and 7.6% respectively, there were no significant differences in three loci(p>0.05). The total positive rate was 7.6%; in tumor tissue, the positive rate in these loci was 2.6%, 0% and 7.9%, there were no significant differences, either (p>0.05). The total positive rate was 7.5%, and no significant difference was showed with the total positive rate in dysplasia tissue (p>0.05). There was correlation between LOH in dysplasia tissue and that in tumor tissue (p<0.05).3. IHC resultsRespectively, the positive rate of hMLHl protein expression in normal tissue, dysplasia tissue and tumor tissue was 90%, 57.6% and 45%, which showed significant differences between lesion tissue (including dysplasia and tumor tissue) and normal tissue (p<0.05). Meanwhile, in dysplasia tissue and tumor tissue, hMLHl protein were also found in cytoplasm beside in karyon with positive rate of 38.5% and 50%, which was higher than that in normal tissue (7.5%) significantly.4. Relationship between MSI and IHC resultsIn dysplasia tissue, the correlation between MSI and defect of hMLHl protein expression in karyon was found (p<0.05), but the same correlation was not found in tumor tissue (p>0.05).5. Relationship between LOH and IHC resultsThere was no correlation was proved between LOH of hMLHl gene and hMLHl protein expression in both dysplasia tissue and tumor tissue (p>0.05).6. Relationship between MSI and clinicopathological parameters There was no correlation between MSI of tumor tissue and any ofclinicopathological parameters including age, sex of patients, invasion depth, grade of tumor and the status of lymph node metastasis (p>0.05).7. Relationship between LOH and clinicopathological parameters There was no correlation between LOH of hMLHl gene and any ofclinicopathological parameters i...
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