The Relationship Among The Expression Of Tjymidylate Synthase, Thymidine Phosphorylase And Dihydropyrimidine Dehydrogenanse And The Prognosis Of Breast Cancer Patients

Objectives: As a common malignant neoplasm of women, the epidemiologicalcharacteristics of breast cancer was that the incidence rate is keeping increasing and more and more young women were affected by this disease, metastasis in early stage was also easily occurred and which was thought the main reason for the death of patients. So early diagnosis and proposal comprehensive therapy were critical for the long survival of breast cancer patients.Thymidylate synthase (TS) is composed of dimmer of two same subunits with molecular weight of 36KD and the function was to catalyse the methylation of dUMP so to form Dtmp, and it was the restricting enzyme in the synthesis of Dtmp and exerts the critical role in the G1 and S phase of cell cycle. Thymidine Phosphorylase (TP) was an enzyme of the pyrimidine nucleoside phosphorylase family, and it was a endothelial cell growth facor detivated from platelet. Dihydropyrimidine Dehydrogenase (DPD) is the rate limiting enzyme of the initial degradation fo 5-Fu, which convert 5-Fu to an inactive agent. The activity of DPD in liver, which was the main viscera of degradation of 5-Fu, was the highest, and in other tissue, its activity could also be detected.Now, the size of tumor, status of lymphatic metastasis, histological grade and the expression of hormone receptor were used as the important indicies of prognosis of breast cancer patients. In past decade, the expression of TS, TP and DPD were thought to related with the effect of 5-Fu chemotherapy in colorectal cancer patients,and in recent years, many peoples found that the expression of these were related with the prognosis of colorectal cancer patients, so most of the studies were concentrated in this point. But studies about this topic in breast cancer patients was rare.So the purpose of this study was to detect the expression of TS, TP and DPD and the microvascular density, relationships between these with the indicies such as the effect of adjuvant chemotherapy, 10 year survival rate and 10 year disease free survival rate, and as a result to define a new and effective index for the determination of prognosis and effect of therapy.Methods: To detect the expression of TS, TP, DPD and the angiogenesis factor CD31 in breast cancer tissue with the method of immunohistochemistry (ABC). Results:1 .There is significant relationship between MVC and the size of tumor, the status of axillary lymph node and the histological grade, and the MVC was not affected by the ages and the expression of sexal hormone receptors. The 10 year disease free syrvival rate of MVC positive patients was 1.31%, which was significantly lower than that of the patients with that of MVC negative patients, 23.68%, (pO.Ol). In the view of the overall survival rate, the overall 10 year survival rate of MVC positive patients was 15.35%, which was significantly lower than that of the MVC negative patients(73.68%, pO.Ol)2 .There was obvious relationship between the expression of TS and the size of tumor, lymphatic status and the histological grade and the MVC, but there was no significant relationship among the age and expression of ER and PR. The 10 year disease free survival rate in TS positive patients was 0, but that of the TS negative patients was 25%, which was significantly higher than that of the TS positive patients(p<0.01). From the viewpoint of overall survival rate, the 10 year overall survival rate of TS positive patients was 58.77%, which was significantly higher than that of the TS positive patients (3.94%, pO.Ol)3 .There was obvious relationship between the expression of TP and the size of tumor, lymphatic status and the histological grade and the MVC, but there was no significantrelationship among the age and expression of ER and PR. The 10 year disease free survival rate in TP positive patients was 0, but that of the TP negative patients was 25.44%, which was significantly higher than that of the TP positive patients(p<0.01). From the viewpoint of overall survival rate, the 10 year overall survival rate of TP positive patients was 61.84%, which was significantly higher than that of the TS positive patients (0.88%, pO.Ol)4. The expression of DPD was not related with the so many pathoclinical features such as age of patient, size of tumor, lymphatic status, expression of ER and PR and MVC. The 10 year disease free survival rate and overall survival rate of DPD negative and positive patients were 16.23%, 8.77%, 39.47% and 23.25% respectively and there were no significantly statistical difference(p>0.05). So the expression of DPD was not related to the 10 year disease free survival rate and overall survivial rate.5. Based on multiple factor analysis, we found that (1) there were significant relationship among the histoligical grade, lymphatic status, MVC, expression of TS and the disease free survival rate, and the OR of MVC and TS were all smaller than 1(0.559 and 0.128 respectively), that is to say that these two were strong protective factors for disease free survival rate, which means that the lower MVC and expression of TS, the longer the disease free survival of patients. (2) The histological grade, lymphatic status, expression of TS and TP were all related with the overall survival rate, the OR of TS, TP were 0.379 and 0.219 respectively, so these two were also strong protective factors for the overall survival rates.Conclusions:1 The level of expression of TS may be an important prognostic index for breast cancer patients,2 There was relatinship between the expression of TP and the 10 year overall survival rate, the levels of TP and MVC can not only affect the 10 year disease free survival rate and overall survival rate, the expression of TP was also related to that of the MVC.3 Based on the results of this study, we did not find any relationship among the expression of DPD with any pathoclinical characteristics and 10 year disease freesurvival rate and overall survival rate.AIMS: With the increase of 10 year survival rate of breast cancer patients, the breast preserving operation for breast cancer was accepted by more and more surgeons and patients, but how to increase the successful rate and improve the quality of life were also important questions for both surgeons and patients.It was well known that the pathogenesis and development of breast cancer was a complicated progress affected by many factors, and it was a local manifestation of systemic disease. As more and more young patients appeared and systemic micrometastasis occurred in early stage in many patients, the systemic preoperative chemotherapy(neoadjuvant chemotherapy) was not only effective in eradicating the systemic micrometastasis , it can also to decrease the clinical pathological stage so to increase the successful rate of breast preserving operation.To date, 5-Fu is also an necessary drug for chemotherapy of breast cancer, and 5-Fu base regimen such as CMF, CAF, CEF were classical regimen for this disease. But until today, there is not a effective for selection of patients which were sensitive for 5-Fu based regimen, and the feasibility of TS, TP and DPD for this purpose was still in study.In this study, we detect the expression of TS, TP, DPD and C-erbb2, combined with the effect of neoadjuvant chemotherapy , so to evaluate the relationship among the effect of neoadjuvant chemotherapy and the expression of TS, TP and DPD, so to...