Huang C L, Yokomise H, Kobayashi S, Fukushima M, Hitomi S, Wada H
The Second Department of Surgery, Kagawa Medical University, Japan.
Int J Oncol. 2000 Jul;17(1):47-54.
5-fluorouracil (5-FU) has been used widely, including in gastrointestinal cancer, breast cancer, and non-small cell lung cancer (NSCLC), and its efficacy has been reported to be associated with intratumoral expression of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD). In order to clarify the clinical value of their expression in NSCLC patients treated with 5-FU, we investigated intratumoral expression of TS and DPD immunohistochemically. Of the 68 tumors studied, 40 carcinomas (58. 8%) had high TS expression, and 33 carcinomas (48.5%) had high DPD expression. The 5-year survival rate of the patients with high-TS tumors was significantly lower than that of the patients with low-TS tumors (P=0.0267), and the 5-year survival rate of the patients with high-DPD tumors was significantly lower than that of the patients with low-DPD tumors (P=0.0268). The Cox regression analysis of prognostic variables for NSCLC patients treated with 5-FU demonstrated that the simultaneous evaluation for both TS and DPD expression was found to be a significant indicator of a poor prognosis (P=0.0043). Our results demonstrated that the evaluation of intratumoral TS and DPD activity can be used to accurately predict responsiveness to 5-FU-based chemotherapy in NSCLC patients.
5-氟尿嘧啶（5-FU）已被广泛应用，包括用于治疗胃肠道癌、乳腺癌和非小细胞肺癌（NSCLC），据报道其疗效与肿瘤内胸苷酸合成酶（TS）和二氢嘧啶脱氢酶（DPD）的表达有关。为了阐明它们的表达在接受5-FU治疗的NSCLC患者中的临床价值，我们采用免疫组织化学方法研究了肿瘤内TS和DPD的表达。在所研究的68个肿瘤中，40个癌（58.8%）有高TS表达，33个癌（48.5%）有高DPD表达。高TS肿瘤患者的5年生存率显著低于低TS肿瘤患者（P = 0.0267），高DPD肿瘤患者的5年生存率显著低于低DPD肿瘤患者（P = 0.0268）。对接受5-FU治疗的NSCLC患者的预后变量进行Cox回归分析表明，同时评估TS和DPD表达是预后不良的一个重要指标（P = 0.0043）。我们的结果表明，评估肿瘤内TS和DPD活性可用于准确预测NSCLC患者对基于5-FU的化疗的反应性。
