Topoisomerase I but not thymidylate synthase is associated with improved outcome in patients with resected colorectal cancer treated with irinotecan containing adjuvant chemotherapy
Topoisomerase I but not thymidylate synthase is associated with improved outcome in patients with resected colorectal cancer treated with irinotecan containing adjuvant chemotherapy
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DOI：
10.1186/1471-2407-9-339
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发表时间：
2009-09-24
期刊：
影响因子：
3.8
通讯作者：
Fountzilas, George
中科院分区：
文献类型：
--
作者：
Kostopoulos, Ioannis;Karavasilis, Vasilios;Fountzilas, George
背景：胸苷酸合成酶（TS）和拓扑异构酶I （Topo I）是结直肠癌（CRC）的重要生物标志物。我们的目的是研究TS和Topo I在接受辅助化疗的结直肠癌切除患者中的表达，并将其与临床结果联系起来。方法：所有在1989年至2007年间诊断为结直肠癌并在希腊肿瘤合作组织（Hellenic Cooperative Oncology Group, HeCOG）方案下接受辅助化疗的患者。采用档案石蜡包埋的肿瘤组织对TS和Topo i进行免疫组化检测，使用抗TS和Topo i的单克隆抗体对组织微阵列载玻片进行免疫组化检测，结果与生存（OS）和无病生存（DFS）相关。结果：498例患者中位年龄61岁，Dukes分期为B期（49%）和C期（51%），符合研究标准。所有患者均接受以5- fu为基础的辅助化疗，含伊立替康38%。TS和Topo I阳性表达分别占43%和48%。5年OS为74%，DFS为68%。在单因素分析中，没有发现TS和Topo I表达与OS和DFS的关联。然而，在多变量分析中，Topo I表达与死亡风险降低相关（HR = 0.61, 95% CI 0.42-0.88, p = 0.009）。在伊立替康治疗亚组中，表达Topo I的患者有更好的OS （HR = 0.47, 95% CI 0.23-0.94, p = 0.033）。结论：表达Topo I的结直肠癌切除患者似乎受益于含伊立替康的辅助化疗。然而，需要随机前瞻性试验来证实这些结果。
Background: Thymidylate synthase (TS) and Topoisomerase I (Topo I) are significant biomarkers in colorectal cancer (CRC). We aimed to study the expression of TS and Topo I in patients with resected CRC who received adjuvant chemotherapy and correlated it with clinical outcome.Methods: All patients diagnosed with CRC between 1989 and 2007 and treated with adjuvant chemotherapy within Hellenic Cooperative Oncology Group's (HeCOG) protocols, were identified. Archival paraffin-embedded tumor tissues were used for immunohistochemical detection of TS and Topo I. Immunohistochemistry was performed on tissue microarray slides using monoclonal antibodies against TS and Topo I. The results were correlated with survival (OS) and disease free survival (DFS).Results: A cohort of 498 patients with a median age of 61 years and Dukes' stage B (49%) and C (51%) fulfilled the criteria of the study. All patients received adjuvant 5-FU-based chemotherapy, 38% irinotecan-containing. Positive TS and Topo I expression was found in 43% and 48% of cases, respectively. Five-year OS was 74% and DFS was 68%. In univariate analysis no association of TS and Topo I expression with OS and DFS was identified. In multivariate analysis however, Topo I expression was associated with a reduced risk of death (HR = 0.61, 95% CI 0.42-0.88, p = 0.009). In the irinotecan-treated subgroup, those patients who expressed Topo I had a better OS (HR = 0.47, 95% CI 0.23-0.94, p = 0.033).Conclusion: Patients with resected CRC expressing Topo I seem to benefit from irinotecan-containing adjuvant chemotherapy. However randomised prospective trials are needed to confirm these results.