Clinical Relevance of Microsatellite Instability in Colorectal Cancer

被引:264
作者
de la Chapelle, Albert [1 ]
Hampel, Heather [1 ]
机构
[1] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA
关键词
DNA MISMATCH REPAIR; HMLH1 PROMOTER HYPERMETHYLATION; LYNCH-SYNDROME; COLON-CANCER; ADJUVANT CHEMOTHERAPY; YOUNG-PATIENTS; CELL-LINES; MONONUCLEOTIDE REPEATS; BETHESDA GUIDELINES; REPLICATION ERRORS;
D O I
10.1200/JCO.2009.27.0652
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Microsatellite instability (MSI) is a clonal change in the number of repeated DNA nucleotide units in microsatellites. It arises in tumors with deficient mismatch repair due to the inactivation of one of the four mismatch repair genes: MSH2, MLH1, MSH6, and PMS2. In order to determine the MSI status of a tumor, microdissection and polymerase chain reaction-based detection strategies are required. For practical purposes, MSI is equivalent to the loss of staining by immunohistochemistry (IHC) of one of the mismatch repair genes since both signify an abnormality in mismatch repair. Of all colorectal cancers (CRCs), 15% to 20% display MSI or abnormal IHC (often referred to as microsatellite instability [MIN] pathway). The remaining 80% to 85% of CRCs are microsatellite stable but most are characterized by chromosomal instability (CIN pathway). Almost all Lynch syndrome tumors have MSI or abnormal IHC and they account for up to one third of all MIN CRCs (3% to 5% of all CRCs). The remaining MIN tumors are sporadic as a result of somatic inactivation of the MLH1 gene caused by methylation of its promoter. Thus, the presence of a MSI/IHC abnormality prompts further investigations to diagnose Lynch syndrome, whereas its absence excludes Lynch syndrome. We recommend screening all CRC tumors for IHC or MSI. MIN tumors have a more favorable outcome than CIN tumors, and fluorouracil-based adjuvant chemotherapy does not improve the outcome of stage II or stage III MIN tumors. More data are needed to determine how best to treat patients with stage II and stage III MIN CRCs. J Clin Oncol 28:3380-3387. (C) 2010 by American Society of Clinical Oncology
引用
收藏
页码:3380 / 3387
页数:8
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