Fallik D, Sabourin J C, Borrini F, Jacob S, Boige V, Praz F, Ducreux M
Laboratoire CNRS UMR 1598, Service de Gastroentérologie, Institut Gustave-Roussy, Camille-Desmoulins, Villejuif.
Gastroenterol Clin Biol. 2000 Oct;24(10):917-22.
The aim of our study was to assess the potential relationships between tumor responsiveness to CPT11, an analogue of camptothecin, which selectively inhibits DNA topoisomerase I, and the microsatellite instability, a feature of tumors with DNA mismatch repair defect.
We designed a retrospective clinical study including 35 patients with metastatic colorectal cancer treated with CPT11, for which we analyzed the expression of hMLH1 and hMSH2 in the tumor and determined microsatellite status of repeated mononucleotide tracts present in the coding region of RII-TGFB, BAX, hMSH3 and hMSH6 genes.
A partial or minor response was observed in 9 patients, disease stabilization in 14 patients and progression in 12 patients. Staining of hMLH1 was undetectable in 2 of the 35 tumors, while only 1 tumor lacked hMSH2 expression. Four of the 31 tumors analyzed displayed intragenic microsatellite instability. We found a good correlation between inactivation of TGFB-RII, BAX or hMSH3 genes and tumor response to CPT-11 (P =0.002).
Our preliminary data suggest that intragenic microsatellite instability may influence tumor response to CPT-11 in patients with colorectal cancer.
我们研究的目的是评估喜树碱类似物CPT11（其选择性抑制DNA拓扑异构酶I）的肿瘤反应性与微卫星不稳定性（DNA错配修复缺陷肿瘤的一个特征）之间的潜在关系。
我们设计了一项回顾性临床研究，纳入35例接受CPT11治疗的转移性结直肠癌患者，分析其肿瘤中hMLH1和hMSH2的表达，并确定RII-TGFB、BAX、hMSH3和hMSH6基因编码区存在的重复单核苷酸序列的微卫星状态。
9例患者观察到部分或轻微反应，14例患者疾病稳定，12例患者疾病进展。35个肿瘤中有2个未检测到hMLH1染色，而只有1个肿瘤缺乏hMSH2表达。分析的31个肿瘤中有4个显示基因内微卫星不稳定性。我们发现TGFB-RII、BAX或hMSH3基因失活与肿瘤对CPT-11的反应之间存在良好相关性（P = 0.002）。
我们的初步数据表明，基因内微卫星不稳定性可能影响结直肠癌患者对CPT-11的肿瘤反应。
