Yu Z, Sun J, Zhen J, Zhang Q, Yang Q
Department of Surgery, the Second Affiliated Hospital of Shandong University, Ji'nan, Shandong Province, People's Republic of China.
Histol Histopathol. 2005 Jul;20(3):871-8. doi: 10.14670/HH-20.871.
Thymidylate synthase (TS) is a major target of 5-fluorouracil (5-FU) and dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme in the degradation of 5-FU. Whether TS or DPD could be used as valuable parameters for 5-FU sensitivity in clinical patients are largely unknown. We analyzed TS and DPD expression in breast carcinomas to evaluate the clinicopathological significance of these enzymes in patients with invasive breast cancer receiving 5-FU-based chemotherapy. A total of 197 patients with invasive ductal carcinoma were included in our study. Both the TS and DPD expression were analyzed using immunohistochemical method for all the surgical samples. Sixty-three out of 197 (31.97%) patients are positive for TS expression, and 77 out of 197 (39.09%) patients are positive for DPD expression. TS expression was not correlated with DPD expression. Patients with TS-positivity had aggressive phenotype including large tumor size, low differentiation and nodal metastasis. DPD expression is not related with phenotype or prognosis. Multivariate analysis demonstrated that TS expression was an independent prognostic factor for both disease-free and overall survival. The current study demonstrated that TS but not DPD expression was associated with both progression and prognosis in breast cancer receiving 5-FU-based chemotherapy. TS expression in the primary tumor might be useful as a predictive parameter for the efficacy of 5-FU-based chemotherapy for breast cancer.
胸苷酸合成酶（TS）是5-氟尿嘧啶（5-FU）的主要作用靶点，二氢嘧啶脱氢酶（DPD）是5-FU降解的限速酶。TS或DPD是否可作为临床患者5-FU敏感性的有价值参数在很大程度上尚不清楚。我们分析了乳腺癌中TS和DPD的表达，以评估这些酶在接受基于5-FU化疗的浸润性乳腺癌患者中的临床病理意义。我们的研究共纳入了197例浸润性导管癌患者。对所有手术样本均采用免疫组织化学方法分析TS和DPD的表达。197例患者中有63例（31.97%）TS表达阳性，197例患者中有77例（39.09%）DPD表达阳性。TS表达与DPD表达无关。TS阳性患者具有侵袭性表型，包括肿瘤体积大、低分化和淋巴结转移。DPD表达与表型或预后无关。多因素分析表明，TS表达是无病生存期和总生存期的独立预后因素。目前的研究表明，在接受基于5-FU化疗的乳腺癌中，TS表达而非DPD表达与疾病进展和预后均相关。原发肿瘤中的TS表达可能作为乳腺癌基于5-FU化疗疗效的预测参数。
