Second Department of Surgery, Showa University School of Medicine, Tokyo 142-8666, Japan.
Oncol Rep. 2010 Mar;23(3):771-7.
New anticancer drugs have been developed, and prediction of their effect is needed to perform tailor made chemotherapy. We investigated a selection of the predictive markers for oral adjuvant chemotherapy among 5-fluorouracil (5-FU) related genes. 5-FU related genes were examined by using a laser captured microdissection and real-time RT-PCR in 220 patients with invasive breast cancer. Sixty-six patients were treated with postoperative oral fluorouracil derivatives for 12 months or more, and we examined the prognosis of these patients according to the expression of 5-FU related genes. The median of thymidylate synthase (TS), dehydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyltransferase (OPRT) mRNA values in the 220 specimens were determined for cut-off levels separating low and high gene expression. In 66 patients, 5-year disease-free survival (DFS) in the TP-high group (n=28) was significantly better than that in the TP-low group (n=38) (P=0.016). Of 220 patients, the 69 patients in TP-high group comprised 28 patients treated with oral fluorouracil derivatives and 41 patients with hormone therapy alone. The proportion of patients with lymph node involvement in the fluorouracil group was significantly greater than that in the hormone therapy alone group (P=0.003). Five-year DFS was not significantly different between the groups (P=0.80). Our results suggest that adjuvant oral fluorouracil chemotherapy may improve the prognosis of the patients with TP high expression breast cancer, and TP mRNA level in breast cancer may predict the effect of new oral fluorouracil derivatives for postoperative adjuvant chemotherapy.
已经开发出了新的抗癌药物，需要对其疗效进行预测，以便进行定制的化疗。我们在 220 名浸润性乳腺癌患者中研究了一组与 5-氟尿嘧啶（5-FU）相关基因的预测标志物。使用激光捕获显微切割和实时 RT-PCR 检查了 5-FU 相关基因。66 例患者接受了术后口服氟尿嘧啶衍生物治疗 12 个月或更长时间，我们根据 5-FU 相关基因的表达情况检查了这些患者的预后。在 220 个标本中确定了胸苷酸合成酶（TS）、二氢嘧啶脱氢酶（DPD）、胸苷磷酸化酶（TP）和乳清酸磷酸核糖基转移酶（OPRT）mRNA 值的中位数，以区分低表达和高表达的水平。在 66 例患者中，TP 高组（n=28）的 5 年无病生存率（DFS）明显优于 TP 低组（n=38）（P=0.016）。在 220 例患者中，TP 高组的 69 例患者包括 28 例接受口服氟尿嘧啶衍生物治疗和 41 例单独接受激素治疗的患者。氟尿嘧啶组淋巴结受累患者的比例明显大于单独激素治疗组（P=0.003）。两组之间的 5 年 DFS 无显著差异（P=0.80）。我们的结果表明，辅助口服氟尿嘧啶化疗可能改善 TP 高表达乳腺癌患者的预后，乳腺癌中 TP mRNA 水平可能预测新的口服氟尿嘧啶衍生物在术后辅助化疗中的疗效。
