胸苷酸合成酶、胸腺嘧啶脱氧核苷磷酸化酶及二氟嘧啶脱氢酶的表达与乳腺癌预后的相关性

目的通过检测乳腺癌标本中胸苷酸合成酶（TS）、胸腺嘧啶脱氧核苷磷酸化酶（TP）、二氟嘧啶脱氢酶（DPD）表达情况,探讨乳腺癌的生物学行为与上述3个指标之间的相关性.方法采用免疫组织化学（ABC法）检测228例乳腺癌组织中TS、TP和DPD的表达情况.结果 TS、TP与患者的肿瘤大小、淋巴结状态、组织学分级及MVC有明显的相关性,与患者的年龄、激素受体状态（ER,PR）无关;DPD的表达与患者的年龄,肿瘤大小,淋巴结状态,激素受体状态（ER,PR）、组织学分级及MVC等诸多临床病理因素均无相关性;TS、TP表达阳性患者的10年无病生存率和总生存率明显低于表达阴性者（0、0、3.9%、0.9%和25%、25.4%、58.8%、61.8%）,具有显著的统计学差异（均P〈0.01）;DPD表达阳性和阴性患者的10年无病生存率和总生存率为8.8%、16.2%、23.3%、39.5%,均无显著性差异（均P〉0.05）.多因素分析发现：组织学分级、淋巴结状态、TS和TP的表达与患者的总生存率都有十分明显的相关性,而且TS和TP的危险系数分别为0.379、0.219,均小于1,这同样说明这两者对于总生存率来说都是非常强烈的保护因素.结论 TS、TP表达水平的高低有可能是乳腺癌患者一个重要的预后指标;DPD的表达与临床病理因素、10年无病生存和总生存率之间无任何相关性.

Relationships among the expression of thymidylate synthase, thymidine phosphorylase, and dihydropyrimidine dehydrogenase and the prognosis of breast cancer

Objective To investigate the relationships among the expression of thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD) and the prognosis of breast cancer.Methods Immunochemistry (ABC method) was used to detect the expression of TS, TP, and DPD in the samples of breast cancer resected during operation from 28 female patients. The microvessel density (MVD) in the cancer tissue was measured by immunochemistry (LSAB method).Results The TS positive rate was 30.26% and the TP positive rate was 21%, and the DPD positive rate was 30.03%. The expression levels of TS and TP were both correlated with the tumor size, lymph node status, histological grading of tumor, and microvessel count (MVC) (all P<0.01), and was not correlated with age, status of estrogrn receptors, status of prosterone receptors (all P>0.05). The DPD expression was not correlated with the age, tumor size, lymph node status, histological grading of tumor, status of estrogrn receptors, status of prosterone receptors, and MVC. The ten-year disease-free survival rate of the TS-positive patients was 0, significantly lower than that of the TS-negative patients (25%, P<0.01). The ten-year overall survival rate of the TS-positive patients was 3.9%, significantly lower than that of the TS-negative patients (58.8%, P<0.01). The ten-year disease-free survival rate of the TP-positive patients was 0, significantly lower than the TP-negative patients (25.4%, P<0.01). The ten-year overall survival rate of the TP-positive patients was 0.9%, significantly lower than that of the TP-negative patients (61.8%, P<0.01). The ten-year disease-free survival rate and ten-year overall survival rate of the DPD positive patients were not significantly different from those of the DPD negative patients (both P>0.05). MCV and TS expression were strong protective factors of disease-free survival rate and overall survival rate.Conclusion The levels of TS and TP are both prognostic indicis of breast cancer.