Yamada H, Ichikawa W, Uetake H, Shirota Y, Nihei Z, Sugihara K, Hirayama R
Department of Digestive Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
Clin Colorectal Cancer. 2001 Nov;1(3):169-73; discussion 174. doi: 10.3816/CCC.2001.n.017.
Thymidylate synthase (TS) expression has been identified as an important predictor of response to 5-fluorouracil (5-FU). However, there is relatively little information on the heterogeneity of TS mRNA expression between primary and metastatic tumors, as well as differential expression of TS mRNA in metastatic sites. In this study, TS mRNA expression was measured in primary colorectal cancer tumors and various metastatic tumors. The median TS/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratio was 0.98 in primary tumors, 0.70 in liver metastases, 1.92 in lymph node metastases, and 3.42 in pulmonary metastases. A significantly higher expression of TS mRNA was observed in pulmonary and lymph node metastases compared with their respective primary tumors. In contrast, TS mRNA expression in hepatic metastases was significantly lower than in primary tumors. Similar results were observed in tumors obtained from the same patient. These results may explain the difference in the clinical response to 5-FU-based chemotherapy between various metastatic sites. The discordant TS expression between primary and metastatic tumors is a critical factor that must be taken into account when TS is being used as a predictive biomarker for the antitumor effect of 5-FU-based chemotherapy.
胸苷酸合成酶（TS）的表达已被确定为对5-氟尿嘧啶（5-FU）反应的重要预测指标。然而，关于原发性肿瘤和转移性肿瘤之间TS mRNA表达的异质性，以及TS mRNA在转移部位的差异表达，相关信息相对较少。在本研究中，我们检测了原发性结直肠癌肿瘤和各种转移性肿瘤中TS mRNA的表达。原发性肿瘤中TS/甘油醛-3-磷酸脱氢酶（GAPDH）mRNA的中位比值为0.98，肝转移灶中为0.70，淋巴结转移灶中为1.92，肺转移灶中为3.42。与各自的原发性肿瘤相比，肺转移灶和淋巴结转移灶中TS mRNA的表达显著更高。相反，肝转移灶中TS mRNA的表达明显低于原发性肿瘤。在同一患者的肿瘤中也观察到了类似的结果。这些结果可能解释了不同转移部位对基于5-FU的化疗临床反应的差异。当TS被用作基于5-FU的化疗抗肿瘤效果的预测生物标志物时，原发性肿瘤和转移性肿瘤之间TS表达的不一致是一个必须考虑的关键因素。
