Thymidylate synthase predicts for clinical outcome in invasive breast cancer.
Thymidylate synthase predicts for clinical outcome in invasive breast cancer.
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DOI：
10.14670/hh-20.871
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发表时间：
2005-07
影响因子：
2
通讯作者：
Zhigang Yu;J. Sun;J. Zhen;Q. Zhang;Qifeng Yang
中科院分区：
文献类型：
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作者：
Zhigang Yu;J. Sun;J. Zhen;Q. Zhang;Qifeng Yang
胸苷酸合成酶（TS）是5-氟尿嘧啶（5-FU）的主要靶标，二氢嘧啶脱氢酶（DPD）是5-氟尿嘧啶降解的限速酶。TS或DPD是否可以作为临床患者5-FU敏感性的有价值的参数在很大程度上是未知的。我们分析了TS和DPD在乳腺癌中的表达，以评估这些酶在接受5- fu化疗的浸润性乳腺癌患者中的临床病理意义。我们共纳入了197例浸润性导管癌患者。采用免疫组织化学方法分析所有手术标本TS和DPD的表达。197例患者中63例（31.97%）TS表达阳性，197例患者中77例（39.09%）DPD表达阳性。TS表达与DPD表达无相关性。ts阳性患者具有侵袭性表型，包括肿瘤大、分化低、淋巴结转移。DPD的表达与表型或预后无关。多变量分析表明，TS表达是无病生存和总生存的独立预后因素。目前的研究表明，在接受5- fu化疗的乳腺癌患者中，TS而非DPD表达与进展和预后相关。TS在原发肿瘤中的表达可能有助于作为基于5- fu的乳腺癌化疗疗效的预测参数。
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.