The Polymorphisms Of The Thymidylate Synthase Gene In Primary Colon Cancer

Part 1. Expression of the thymidylate synthase protein in primary colon cancer and its relationship with clinical pathological parametersObjective:To investigate the relationship between the expression of thymidylate synthase protein and clinical pathological characteristics of primary colon cancer.Methods:The expression of thymidylate synthase protein in surgically resected specimens of 68 colon carcinoma and its corresponding paraneoplastic tissues was determined by immunohistochemistry SP method, and its relationship with their corresponding clinical data was analyzed.Results:The positive expression rate of thymidylate synthase protein in colon cancer and its corresponding paraneoplastic tissues was 94%(64/68)、84%(57/68) respectively, and there was statistically significant difference between the two groups (P<0.05). No correlation was found in expression levels of thymidylate synthase protein with their clinicopathological features such as sex, age, tumor site, tumor long diameter and histological type (P>0.05). The positive expression rate of thymidylate synthase protein in colon cancer of high differentiation degree was less than that in moderate and low differentiation degree (P= 0.026, P<0.05). The positive expression rate of thymidylate synthase protein in colon cancer of Dukes stage A was less than that in Dukes stage B and C (P= 0.021, P<0.05).The positive expression rate of thymidylate synthase protein in colon cancer of TNMⅢwas more than that in TNMⅠandⅡ(P= 0.021, P<0.05).The positive expression rate of thymidylate synthase protein in colon cancer with tumor invasion was higher than that in colon cancer without tumor invasion.Conclusion:The expression levels of thymidylate synthase protein in colon cancer was not associated with age, sex, tumor site.Thymidylate synthase expression was significantly correlated with histological grading and the depth of tumor invasion. There may be existed the mechanism of coordination in generation and progression of colon cancer. Expression level of thymidylate synthase protein was associated with lymph node metastasis and clinical stage.Thymidylate synthase protein expression is usefull factor related to judge the prognosis in colon cancer.Part 2. Polymorphisms of the thymidylate synthase gene in primary colon cancer and its relationship with clinical pathological parametersObjective:To investigate the relationship between polymorphisms in the thymidylate synthase gene and clinical pathological characteristics of primary colon cancer.Methods:The polymorphism of thymidylate synthase gene in surgically resected specimens of 68 colon carcinoma and its corresponding paraneoplastic tissues was detected by polymerase chain reaction method, and its relationship with their corresponding clinical data was analyzed.Results:There were three genotypes of thymidylate synthase gene including homozygous with double tandem repeats (2R/2R), homozygous with triple tandem repeats (3R/3R) and heterozygous with both alleles (2R/3R) in 68 cases of colon cancer (6,40,22 cases respectively). No correlation was found between the three genotypes of thymidylate synthase gene with their clinicopathological features such as sex, age, tumor site, tumor long diameter, general type and histological type (P>0.05) 3R/3R type existed more than the other two types with the depth of tumor invasion, clinical stage and lymph node metastasis (P<0.05). IRS (immunoreactivity score) of 3R/3R type was higher than it in 2R/3R type (5.73±3.25,3.77±2.64 respectively, P= 0.015, P<0.05). IRS of 3R/3R type was higher than it in 2R/2R type (5.73±3.25, 2.17±1.47 respectively, P= 0.008, P<0.05). There was no statistically difference of IRS between 2R/3R type and 2R/2R type (P= 0.243, P>0.05)Conclusion:There were three genotypes of thymidylate synthase gene including homozygous with double tandem repeats (2R/2R), homozygous with triple tandem repeats (3R/3R) and heterozygous with both alleles (2R/3R) in 68 cases of colon cancer(6,40,22 cases respectively). There was statistically difference between 3R/3R and 2R/2R,2R/3R in the depth of tumor invasion, clinical stage and lymph node metastasis. The colon cancer with 3R/3R genotype was liable to tumor invasion and lymph node metastasis.Part 3. Expression of the thymidylate synthase protein in primary colon cancer and its relationship with malignant proliferation, apoptosisObjective:To investigate the relationship between expression of the thymidylate synthase protein and malignant proliferation, apoptosis of primary colon cancer.Methods:Immunohistochemistry SP method was used to determine the expression of proliferating cell nuclear antigen (PCNA) and thymidylate synthase protein, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used to detect cell apoptosis in surgically resected specimens of 68 colon carcinoma and its corresponding paraneoplastic tissues. The relationship between immunoreactivity score of thymidylate synthase with proliferative index(PI)and apoptotic index(AI)was analyzed.Results:No correlation was found between the ratio of proliferative index and apoptosis index with their clinicopathological features such as sex, age, tumor site, tumor long diameter, general type and histological type (P>0.05). There was a positive correlation between immunoreactivity score of thymidylate synthase protein and PI、AI and PI/AI ratio (r=0.816、0.293、0.426, P<0.05)Conclusion:The colon cancer with high expression of thymidylate synthase protein with higher PI and result in increasing the PI/AI ratio.