The Relation And Significance About Expression Of P53、γ-H2AXand TP And Kras Mutations In Sporadic Colorectal Cancer

Background:there is an upward trend in the incidence of colorectal cancer, and has been ranked third among malignant tumors.90%of colorectal cancer is Sporadic colorectal cancer. It is mainly due to the instability of genes, the activation of oncogenes (e.g. K-ras) and the inactivation of cancer suppressor genes (e.g. p53, APC). In addition, DNA damage is also one of the important reasons for malignant tumor. Double-strand break is the most serious damage of DNA damage. And as repair protein, gamma H2AX (gamma histone family2a variant) not only can identify and repair DSB, but also can interact with P53. So, in this way, they can ensure the correctness of DNA genetic information together. Adjuvant chemotherapy has become a popular therapy in patients with colorectal cancer. And5-FU, which is the first choice of chemotherapeutics, is replaced by5-FU precursor drugs oxaliplatin (such as card times he marina) because of its high toxicity. Thymidine Phosphorylase (Thymidine Phosphorylase, TP) is one of the key enzymes of pyrimidine nucleoside metabolism. TP can change5-FU precursor drugs into5-FU and improve the sensitivity of patients in chemotherapy. In this paper, the author has adopted the method of immunohistochemical method to detect the expression of p53, gamma-H2AX and TP in sporadic colorectal cancer, and hsa explored their roles in the occurrence of sporadic colorectal cancer. The last but not least, it can offer help for the patients with sporadic colorectal cancer who need chemotherapy.Objective:1. To observe the expression of p53, gamma H2AX and TP in sporadic colorectal cancer and tissue adjacent to carcinoma, and find clinical pathological meaning of p53, gamma H2AX with TP.2. To find the relevance between the expression of p53, gamma-H2AX and TP and kras in sporadic colorectal cancer, and evaluate the feasibility of p53, gamma H2AX and TP which are chemotherapy sensitivity patients.Method:Using immunohistochemistry to detect the expression of p53γ-H2AX and TP of35patients with sporadic colorectal cancer and15cases of tissue adjacent to carcinoma,. Then,analyzing the relationship of the expression and the clinical pathological features, such as the patients’age, gender, tumor size, degree of differentiation, lymph node metastasis, distant metastasis, clinical stages. Third, analyzing the relation between their expression and kras mutation.Results:P53、 gamma-H2AX and TP in sporadic colorectal cancer expression positive rate were40%,22.9%and62.9%, P53、gamma-H2AX and TP in tissue adjacent to carcinoma expression positive rate were6.67%,13.3%and0%.The expression of P53in sporadic colorectal cancer with tumor size, degree of differentiation of the cancer, and correlated with lymph node metastasis, distant metastasisand clinical stage (p<0.05); Gamma-H2AX expressed in sporadic colorectal cancer and age、tumor size、differentiation degree of cancer tissue、 correlated with lymph node metastasis、 distant metastasis and clinical stage (p<0.05). The expression of TP have no correlation with thepatient age, tumor size, location, cancerous tissue differentiation degree and lymph node metastasis, distant metastasis, clinical stage (p>0.05). Kras wild and TP negative merger of p53positiveafter chemotherapy, the gamma-H2AX positie survival time is short, three years of surviva rateislow.Conclusion:I.p53and gamma-H2AX has played a synergistic role in the development of colorectal cancer. p53, gamma-H2AX positive expression of sporadic colorectal cancer has stronginvasion, easy metastasis, and poor prognosis. They can become one of the significant prognosticindicators;2. Gamma-H2AX positive expression in patients with sporadic colorectal cancer may reflect the drug resistance to chemotherapy.3. Kras wild merger of p53and gamma-H2AX negative, TP positive expression have postoperative chemotherapy,3year survival rate is high, It would become a sensitive predictor of sporadic colorectal cancer patients with chemotherapy.