The MRNA And Protein Expressions Of TP, TS, DPD And Their Correlation With The Clinicopathological Factors And Prognosis In Breast Carcinoma.

Thymidine phosphorylase (TP), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are important enzymes in the metabolism of nucleotide. They also affect therapeutical effect of 5-flurouracil (5-FU) through their interaction with 5-FU.TP can catalyze reversible transformation of the thymidine to deoxyribose-1 -phosphate and thymine, thus stabilize the level of thymidine, which is the essential material for DNA synthesis. The drug 5-FU cannot exert its antitumor function until it is activated by TP in human body. In addition, TP is also involved in the angiogenesissince it is the product of the gene, which makes PD-ECGR..TS is a rate-limiting enzyme in the synthesis of the thymidine and converts dUMP into dTMP, the only source of thymidine for DNA synthesis and repair. Thus, TS plays an important role in the cell division and proliferation. TS is also the target enzyme of 5-FU, which exerts its antitumor activity through its inhibition of TS.DPD is the first rate-limiting enzyme in the catabolism of uracil and thymine, and affects DNA synthesis by decreasing the level of uracil and thymine, the necessary material for DNA synthesis. DPD is also the most important rate-limiting enzyme in the degradation of 5-FU, and catabolize approximately 85% of the 5-FU in vivo.Based on their functions in the metabolism of nucleotide and 5-FU, it is reasonable to predict that TP, TS, and DPD would affect the biological behavior of tumor, therapeutical effect of 5-FU and the prognosis of patients. Investigation on expression of these enzymes in tumors would provide us with valuable data to identify more effective treatment of cancers. In fact, significant difference in expression of TP, TS, and DPD has been observed between tumor and normal tissues. However, those studies were limited to the colorectal cancer and did not explore the correlation between expressions of TP, TS, and DPD.Breast carcinoma is one of the most common malignant tumors,which greatly affects human health and life. It is estimated that 1.2 million of female will be diagnosed of breast carcinoma, with 0.5 million death annually in the world. The incidence of breast cancer is increasing, with an annual rate of approximately 2%. The prevention and effective treatment of breast cancer remain urgent and challenging tasks.The treatment of breast carcinoma has been shifted from surgery only to multidisciplinary therapies, include chemotherapy and endocrinotherapy. Such shift has extended the indications and reduced the extent of surgery for breast cancer. The chemotherapy of breast cancer has been standardized, the effect, however, has not shown a significant improvement. It is hypothesized that individualized chemotherapy would be more promising in the treatment of the tumor. Since 5-FU is the key drug in the chemotherapy of breast cancer, understanding the interaction between 5-FU and expression of TP, TS, and DPD may lead us to find clues for individualizing chemotherapy of breast cancer patients. Recent studies have checked expression of single enzyme among TP, TS, and DPD in tumor with immunohistochemical (IHC) stains. In this study, both mRNA and protein expressions of TP, TS, and DPD were simultaneously examined with real-time quantitative PCR, half- quantitative RT-PCR and IHC stains in 86 Sweden and 93 Chinese breast cancer patients.Geographical difference in expression of TP, TS, and DPD was compared between Sweden and Chinese breast cancer patients. The correlation between expression of the mRNA and protein of these three enzymes and clinicopathological factors such as lymph node status, tumor size, histological grade, clinical and pathological stage, s-phase fraction, survival etc. was explored. The potential roles of three enzymes in the development of breast carcinoma were also discussed.Part oneThe mRNA and protein expressions of TP, TS, DPD and their correlation with the clinicopathological factors and prognosis in breast carcinoma of Sweden female.Materials and Methods:1. Real-time PCR was used to q...