Kim Hee C, Kim Chang N, Yu Chang S, Roh Seon A, Kim Jin C
Department of Surgery, University of Ulsan College of Medicine and Laboratory of Cancer Biology and Genetics, Asan Institute for Life Sciences, 388-1 Poongnap-Dong, Songpa-Ku, Seoul 138-736, Korea.
Int J Colorectal Dis. 2003 May;18(3):196-202. doi: 10.1007/s00384-002-0445-0. Epub 2002 Nov 30.
Microsatellite instability (MSI) occurring from defects in mismatch repair has been found to be associated with about 15% of sporadic colorectal carcinomas. This study examined the incidence of MSI in early-onset sporadic colorectal carcinomas and the role of methylation of the hMLH1 and hMSH2 promoter in sporadic colorectal carcinoma presenting with MSI.
MSI in 38 early-onset and 40 late-onset sporadic colorectal carcinomas were determined as MSI-H, MSI-L, and MSS using five markers. Methylation of the promoter region in hMLH1 and hMSH2 was assessed using methylation-specific PCR (MSP). Their protein expressions were also identified on immunohistochemical staining.
MSI-H, MSI-L, and MSS were found in six (15.8%), three (7.9%), and 29 (76.3%) cases, respectively, in the early-onset group, and in one (2.5%), five (12.5%), and 34 (85%) cases in the late-onset group. Five cases (71.4%) of MSI-H and two cases (25%) of MSI-L showed methylation of the promoter region in hMLH1. No cases with methylation of the promoter region expressed the hMLH1 protein. Only one case of MSI-H showed methylation of the promoter region in hMSH2 with lack of expression of hMSH2.
The mutator pathway in colorectal carcinogenesis appeared more frequently in early-onset than in late-onset colorectal carcinoma. Many cases with MSI in sporadic colorectal carcinoma may be associated with methylation of the promoter in hMLH1.
已发现由错配修复缺陷导致的微卫星不稳定性（MSI）与约15%的散发性结直肠癌相关。本研究检测了早发性散发性结直肠癌中MSI的发生率以及hMLH1和hMSH2启动子甲基化在伴有MSI的散发性结直肠癌中的作用。
使用五个标记物将38例早发性和40例晚发性散发性结直肠癌中的MSI确定为高度微卫星不稳定（MSI-H）、低度微卫星不稳定（MSI-L）和稳定（MSS）。采用甲基化特异性PCR（MSP）评估hMLH1和hMSH2启动子区域的甲基化情况。通过免疫组织化学染色鉴定它们的蛋白表达。
早发性组中分别有6例（15.8%）、3例（7.9%）和29例（76.3%）为MSI-H、MSI-L和MSS，晚发性组中分别有1例（2.5%）、5例（12.5%）和34例（85%）为MSI-H、MSI-L和MSS。5例（71.4%）MSI-H和2例（25%）MSI-L显示hMLH1启动子区域甲基化。启动子区域甲基化的病例均未表达hMLH1蛋白。仅1例MSI-H显示hMSH2启动子区域甲基化且hMSH2表达缺失。
结直肠癌发生中的突变途径在早发性结直肠癌中比在晚发性结直肠癌中更频繁出现。散发性结直肠癌中许多MSI病例可能与hMLH1启动子甲基化有关。
