胸苷磷酸化酶作为乳腺癌治疗靶标的临床研究

目的：研究胸苷磷酸化酶（TP）在乳腺癌组织中的表达及其作为乳腺癌治疗靶标的可能性，同时探索TP在以5-FU为基础的化疗中化疗敏感性的预测作用。方法：采用免疫组化法，检测72例乳腺癌病例及15例良性乳腺肿瘤组织和15例正常乳腺组织中TP的表达，分析其与临床病理参数的关系。并在行含5-FU方案化疗的乳腺癌亚群中分析TP表达对预后的影响。结果：乳腺癌组织中TP表达高于正常乳腺组织和乳腺良性肿瘤组织。TP在不同年龄、病理类型、TNM分期和淋巴结转移和ER、PR和C-erbB-2中表达差异无统计学意义（P〉0．05），与高组织学分级及P53表达有关。在行含5-FU方案化疗的乳腺癌亚群中进行生存分析，TP阳性组与TP阴性组的5年总生存率差异有统计学意义（P〈0．05）。结论：TP在乳腺癌中高表达，与高组织学分级和P53表达有关。在以5-FU为基础的乳腺癌联合化疗中TP阳性组预后较TP阴性组预后为佳，因此TP在以5-FU为基础的乳腺癌联合化疗中可能起到化疗敏感性的预测作用。

Clinical research on Thymidine phosphorylase as therapy target in breast cancer

Objective To investigate the expression of Thymidine phosphorylase(TP) in breast cancer and its possibilities as a therapy target in breast cancer and explore the role of TP in predicting the sensitivity towards chemotherapy based on 5-FU.Methods The expression of TP in 72 breast cancer samples were examined with immunohistochemistry S-P method,15 fibroma samples and 15 normal human breast tissue samples were assessed as control.Differences in the expression of TP in breast cancer were categorized by clinicopathologic characteristics.The effect of expression of TP on prognosis was analyzed in the subgroup of breast cancer patients underwent chemotherapy based on 5-FU.Results The expression of TP in breast cancer was significant different from that in normal breast tissues and benign breast tumors. There were no correlation between the expression of TP and age,pathological type,TNM staging,lymph node metastasis,and C-erbB-2 situation.The expression of TP was negative correlated with higher histological grading and P53.Survival analysis in the subgroup of breast cancer patients underwent chemotherapy based on 5-FU was carried out,in which Log rank test showed a significant difference in 5 year overall survival time between TP positive group and TP negative group (P=0.01).Conclusions TP is overexpressed in breast cancer,and its expression negative correlated with higher histological grading and P53.In the combined chemotherapy based on 5-FU,the prognosis was better in TP positive patients than that in TP negative patients.Therefore,in the combined chemotherapy based on 5-FU,TP might play a role of predicting sensitivity towards chemotherapy.