Immunohistochemical quantitation of thymidylate synthase expression in colorectal cancer metastases predicts for clinical outcome to fluorouracil-based chemotherapy
Immunohistochemical quantitation of thymidylate synthase expression in colorectal cancer metastases predicts for clinical outcome to fluorouracil-based chemotherapy
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DOI：
10.1200/jco.1999.17.6.1760
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发表时间：
1999-06-01
影响因子：
45.3
通讯作者：
Sobrero, A
中科院分区：
文献类型：
--
作者：
Aschele, C;Debernardis, D;Sobrero, A
目的：确定免疫组织化学胸苷酸合酶 (TS) 定量是否可以预测接受氟尿嘧啶 (FUra) 化疗的晚期结直肠癌患者的临床结果。患者和方法：对 48 名接受 FUra 加甲氨蝶呤与连续输注 FUra 加交替同质治疗的患者的结直肠癌转移档案标本进行免疫组织化学测量 TS 水平亚叶酸。这些测量结果与患者特征和临床结果进行回顾性相关。结果：在所有分析的临床结果参数中发现肿瘤内 TS 表达之间存在显着相关性。在肿瘤具有低 (n = 27) 和高 (n = 21) TS 水平的患者中，总体缓解率分别为 67% 和 24% (P = .003)。化疗后肿瘤缩小的百分比与 TS 免疫反应性呈线性相关（r = .56，P = .00004），低 TS 水平和高 TS 水平时其平均值分别为 65% 和 14%（P = .0001）。通过逻辑回归分析，低 TS 表达是化疗反应的单一最佳预测因子（相对概率为 5.0）。在低 TS 表达和高 TS 表达的患者中，中位进展时间分别为 9.6 个月和 6.2 个月 (P = .005)，中位生存时间分别为 18.4 个月和 15.4 个月 (P = .02)。两年和三年生存率分别为 41% vs 15% 和 19% vs 0% (P = .02) 结论：在这一同质治疗患者队列中，肿瘤内 TS 含量是临床结果的主要预测因素。免疫组织化学 TS 定量提供了一种方便、低成本的技术，用于识别对 ta TS 抑制剂无反应的患者，这些患者可能是替代化疗方案的候选者。 (C) 1999 年，美国临床肿瘤学会。
purpose: To determine whether immunohistochemical thymidylate synthase(TS) quantitation predicts for clinical outcome in patients with advanced colorectal cancer heated by fluorouracil (FUra)-based chemotherapy.Patients and Methods: TS levels were measured immunohistochemically on archival specimens of colorectal cancer metastases from 48 patients homogenously treated by bolus FUra plus methotrexate alternating with continuous-infusion FUra plus leucovorin. These measurements were retrospectively correlated with patient characteristics and clinical outcome.Results: A significant correlation was found between intratumoral TS expression find all the parameters of clinical outcome analyzed. In patients whose tumors had low (n = 27) and high (n =21) TS levels, the overall response rates were 67% and 24%, respectively (P = .003). The percentage of tumor shrinkage after chemotherapy was linearly related to TS immunoreactivity (r = .56, P = .00004), and its mean values were 65% and 14% with low and high TS levels, respectively (P = .0001). By logistic regression analysis, low TS expression was the single best predictor of response to chemotherapy (relative probability, 5.0), In patients with low and high TS expression, the median time to progression was 9.6 months v 6.2 months (P = .005) and the median survival time 18.4 months v 15.4 months (P = .02), respectively. Two- and 3-year survival races were 41% v 15% and 19% v 0% (P = .02), respectivelyConclusion: In this cohort of homogenously treated patients, intratumor TS content was a major predictor of clinical outcome. Immunohistochemical TS quantitation provides a convenient, low-cost technique for identifying patients unresponsive ta TS inhibitors who may be candidates for alternative chemotherapy regimens. (C) 1999 by American Society of Clinical Oncology.