Thymidylate synthase protein expression in primary colorectal cancer compared with the corresponding distant metastases and relationship with the clinical response to 5-fluorouracil.
Thymidylate synthase protein expression in primary colorectal cancer compared with the corresponding distant metastases and relationship with the clinical response to 5-fluorouracil.
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发表时间：
2000-12
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通讯作者：
C. Aschele;D. Debernardis;G. Tunesi;F. Maley;A. Sobrero
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作者：
C. Aschele;D. Debernardis;G. Tunesi;F. Maley;A. Sobrero
胸腺苷酸合成酶（TS）在结直肠癌转移中的表达已被证明可以预测5-氟尿嘧啶的临床反应。由于原发肿瘤很容易提供标记物分析的组织来源，我们研究了TS在原发结直肠癌和相应的远端转移癌之间表达的稳定性，并比较了它们预测27例晚期疾病均用生化调节氟尿嘧啶治疗的患者化疗反应的相对能力。通过免疫组化，27例原发肿瘤中有19例（70%）和27例转移性肿瘤中有13例（48%）高水平表达TS。总体而言，原发肿瘤中观察到的TS水平与相应转移瘤中测量到的TS水平不相关（r = 0.30, P = 0.13）， 10例不一致病例中有8例原发肿瘤中TS水平较高。因此，原发肿瘤的TS免疫反应性程度明显高于相应的转移瘤（TS平均评分3.8；中位数为4比2.8；中位数为3；P = 0.001）。原发肿瘤中TS水平高低的患者化疗后的反应率相似（37%对53%，P = 0.47）。相比之下，转移性样品中低TS和高TS患者的缓解率分别为71%和23% （P = 0.012）。总之，原发性结直肠癌中测定的TS水平并不能反映相应转移灶中观察到的TS水平，也不能用于预测其对化疗的反应。原发结直肠癌中TS含量高于相应转移灶的原因有待澄清。
Thymidylate synthase (TS) expression in colorectal cancer metastases has been shown to predict for the clinical response to 5-fluorouracil. Because primary tumors may easily provide accessible sources of tissue for marker analysis, we have investigated the stability of TS expression between primary colorectal cancer and the corresponding distant metastases and compared their relative ability to predict response to chemotherapy on a series of 27 patients homogeneously treated with biochemically modulated fluorouracil for advanced disease. By immunohistochemistry, high levels of TS expression were observed in 19 of 27 (70%) primary tumors and in 13 of 27 (48%) metastatic samples. Overall, TS levels observed in primary tumors did not correlate with those measured in the corresponding metastases (r = 0.30, P = 0.13), with higher TS levels in primary tumors in 8 of 10 discordant cases. Accordingly, the degree of TS immunoreactivity was significantly higher in primary tumors compared with the corresponding metastases (mean TS score 3.8; median, 4 versus 2.8; median 3; P = 0.001). Response rates after chemotherapy for metastatic disease were similar for patients with low and high TS levels in their primary tumors (37% versus 53%, P = 0.47). In contrast, response rates were 71% and 23% in patients with low and high TS in metastatic samples (P = 0.012), respectively. In summary, TS levels measured in primary colorectal cancer do not reflect those observed in the corresponding metastases and cannot be used to predict their response to chemotherapy. The basis for the higher TS content of primary colorectal cancer compared with the corresponding metastases needs clarification.