期刊
DISEASES OF THE COLON & RECTUM
卷 51, 期 9, 页码 1387-1394出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1007/s10350-008-9212-9
关键词
ulcerative colitis-associated colorectal cancer; microsatellite instability; transforming growth factor beta receptor Type II
资金
- Osaka City University Medical Research Foundation
- Kobayashi Foundation for Innovative Cancer Chemotherapy
- Osaka Medical Research Foundation for Incurable Diseases
PURPOSE: Patients with ulcerative colitis have a high risk for the development of colorectal cancer. To understand the molecular mechanisms of the carcinogenesis process of ulcerative colitis-associated colorectal cancer, the genetic alterations in inflamed or neoplastic colon epithelium in ulcerative colitis were analyzed. METHODS: Fifty-seven patients with ulcerative colitis were enrolled in this study. Specimens were obtained from the patients randomly at six colonic sites. Each patient was histologically classified according to the worst pathologic finding into cancer, dysplasia, indefinite, and normal cases. Microsatellite instability, mutations of target genes, hypermethylation of the hMLH1 promoter region, and mismatch repair protein expression were analyzed. RESULTS: High-microsatellite instability was found in 4 of 11 cancer cases (36 percent), 5 of 15 dysplasia cases (33 percent), 5 of 11 indefinite cases (45 percent), and none of 20 normal cases (0 percent). A significant correlation was found between the malignant potential and high-microsatellite instability. A frameshift mutation of transforming growth factor beta receptor Type II (TGF beta RII) was significantly correlated with worsening histologic grade. High-microsatellite instability was significantly associated with hMLH1 hypermethylation and loss of hMSH2 expression. CONCLUSION: The carcinogenesis process in ulcerative colitis-associated colorectal cancer was closely associated with the microsatellite instability pathway through TGF beta RII mutation by a dysfunction of the mismatch repair system.
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