Hee C Kim1, Chang N Kim, Chang S Yu, Seon A Roh, Jin C Kim. 1. 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.
Abstract
BACKGROUND AND AIMS: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND AND AIMS: 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. PATIENTS AND METHODS: 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. RESULTS: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. CONCLUSION: 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.
Authors: In Ja Park; Hee Cheol Kim; Chang Sik Yu; Heung Moon Chang; Jea Hwan Lee; Jong Hoon Kim; Tae Won Kim; Jung Sun Kim; Jin Cheon Kim Journal: Cancer Res Treat Date: 2004-12-31 Impact factor: 4.679
Authors: Hee Cheol Kim; Jin Cheon Kim; Sun Ae Roh; Chang Sik Yu; Jeong Hwan Yook; Sung Tae Oh; Byung Sik Kim; Kun Choon Park; Rin Chang Journal: J Cancer Res Clin Oncol Date: 2005-11-01 Impact factor: 4.553
Authors: M A Mushfiqur Rahman; Tanvir K Chowdhury; Md Akbar Husain Bhuiyan; Md Abdullah Al Farooq; Md Minhajuddin Sajid; Tahmina Banu Journal: Pediatr Surg Int Date: 2014-07-09 Impact factor: 1.827