title: Microsatellite instability and colorectal cancer.
abstract: BACKGROUND
  About 15% of colorectal cancers are characterized by genomic microsatellite instability, and of these, about 1 in 5 (2%-4% overall) are due to Lynch syndrome, a dominantly inherited condition predisposing the patient to cancers of multiple organ systems, including the gastrointestinal tract. Identification of individuals with Lynch syndrome allows for increased surveillance of the affected individual and of potentially affected family members.
  
  
  OBJECTIVE
  To review the literature on microsatellite instability in colorectal cancer and current laboratory diagnostic testing strategies for the detection of Lynch syndrome.
  
  
  METHODS
  This review is based on peer-reviewed literature, published guidelines from professional organizations (Evaluation of Genomic Applications in Practice and Prevention Working Group, National Comprehensive Cancer Network), and information from clinical laboratories performing microsatellite instability testing.
  
  
  CONCLUSIONS
  Universal screening for Lynch syndrome in all individuals affected with colorectal cancer has been recommended by the Evaluation of Genomic Applications in Practice and Prevention Working Group. Preliminary screening tests can identify individuals unlikely to be affected by Lynch syndrome, thereby reducing the need for full gene analysis. Immunohistochemistry and polymerase chain reaction-based tests for microsatellite instability have similar clinical sensitivity and specificity, and each method has advantages and limitations. BRAF and MLH1 methylation testing are useful reflex tests for those with a defect in MLH1 identified by immunohistochemistry. Emerging technologies, such as high-throughput sequencing, may substantially affect diagnostic algorithms in the future.
authors.affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84108, USA. katherine.geiersbach@aruplab.com
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Geiersbach
authors.forename: Wade S
authors.initials: WS
authors.lastname: Samowitz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000465:Algorithms; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D053843:DNA Mismatch Repair / Q000235:genetics; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1