Division of Gastroenterology, Department of Internal Medicine and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, TX 75246, USA.
Aliment Pharmacol Ther. 2009 Sep 15;30(6):634-42. doi: 10.1111/j.1365-2036.2009.04076.x. Epub 2009 Jun 25.
Microsatellite instability (MSI) occurs in chronically inflamed colorectal tissue and may evolve to colitis-associated cancer. In vitro data suggest that mesalazine (5-ASA) improves MSI.
To analyse the changes in MSI in 156 distal colonic biopsies of 39 patients with ulcerative colitis that had been treated within a randomized, double-blind trial comparing 5-ASA with E. coli Nissle (EcN).
Two biopsies had been collected before and after 1 year of treatment. MSI testing was performed using a panel of eight markers, including 3 dinucleotide and 5 mononucleotide repeats.
No MSI was observed with any of the mono-repeats, and among dinucleotide repeats, only D5S346 (maps to APC) and D17S250 (p53) were consistently informative. Overall, 31/156 (20%) biopsies displayed MSI. After 1 year, 3/11 patients displayed MSI improvement [change to microsatellite stability (MSS); 1 on 5-ASA, 2 on EcN] at D5S346 and 4/11 showed MSI worsening (change from MSS to MSI; all 5-ASA). For D17S250, the corresponding data were for 3/9 patients (2 on 5-ASA, 1 on EcN) and 2/9 (both on 5-ASA), respectively.
In the set of biopsies taken from patients treated with 1.5 g 5-ASA for 1 year, there was no improvement in the prevalence of MSI in the distal colon.
微卫星不稳定性 (MSI) 发生在慢性炎症性结直肠组织中,并可能发展为结肠炎相关癌症。体外数据表明美沙拉嗪(5-ASA)可改善 MSI。
分析在溃疡性结肠炎患者的 156 例远端结肠活检中 MSI 的变化,这些患者曾参与一项随机、双盲试验,比较 5-ASA 与大肠杆菌 Nissle(EcN)的疗效。
在治疗 1 年后收集了 2 次活检。使用包含 3 个二核苷酸和 5 个单核苷酸重复的 8 个标记物的面板进行 MSI 检测。
任何单核苷酸重复均未观察到 MSI,在二核苷酸重复中,只有 D5S346(映射至 APC)和 D17S250(p53)始终具有信息性。总体而言,156 个活检中有 31 个显示 MSI。治疗 1 年后,3/11 名患者的 D5S346 处 MSI 改善(从微卫星不稳定(MSS)转为 MSS;5-ASA 治疗组 1 例,EcN 治疗组 2 例),4/11 例显示 MSI 恶化(从 MSS 转为 MSI;均为 5-ASA 治疗组)。对于 D17S250,相应的数据为 3/9 名患者(5-ASA 治疗组 2 例,EcN 治疗组 1 例)和 2/9 名患者(均为 5-ASA 治疗组)。
在接受 1.5 g 5-ASA 治疗 1 年的患者中,远端结肠 MSI 的发生率没有改善。