title: Microsatellite instability in young patients with sporadic colorectal adenomas.
abstract: OBJECTIVE
  This study was designed to determine the prevalence of microsatellite instability (MSI) among colorectal adenomas detected in patients ≤ 40 years of age and to compare the prevalence of MSI in young (≤ 40 years) and older (>40 years) patients with colorectal adenomas. Additionally, we attempted to identify the underlying cause of MSI in these patients.
  
  
  METHODS
  We prospectively tested for the presence of MSI using five NCI markers in samples from the two patient groups. The frequency of MSI was compared and the underlying causes of MSI were determined by methylation specific PCR and germ-line mutation analysis for mismatch repair genes.
  
  
  RESULTS
  The frequency of MSI was higher in the ≤ 40 group than the >40 group (31.4% and 6.4%, respectively, p=0.0004). The MSI-high pattern was also more prevalent in the ≤ 40 group than the >40 group (15.7% and 2.5%, respectively, p=0.014). The hypermethylated hMLH1 gene was demonstrated in 7/8 (87.5%) patients with MSI-high in the ≤ 40 group and in 1/2 (50.0%) patients with MSI-high in the >40 group. No study subject showed a germline mutation of hMLH1 or hMSH2.
  
  
  CONCLUSIONS
  MSI-high was more frequent in young (≤ 40 years) patients with colorectal adenoma than in older (>40 years) patients. Hypermethylation of the hMLH1 gene appears to be an important cause of MSI-high in these patients.
authors.affiliation: Department of Internal Medicine and Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Republic of Korea.
authors.forename: Sung Keun
authors.initials: SK
authors.lastname: Park
authors.forename: Dong Il
authors.initials: DI
authors.lastname: Park
authors.forename: Seung Ha
authors.initials: SH
authors.lastname: Park
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Hong Joo
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yong Kyun
authors.initials: YK
authors.lastname: Cho
authors.forename: Chong Il
authors.initials: CI
authors.lastname: Sohn
authors.forename: Woo Kyu
authors.initials: WK
authors.lastname: Jeon
authors.forename: Byung Ik
authors.initials: BI
authors.lastname: Kim
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Jeong Seon
authors.initials: JS
authors.lastname: Ji
authors.forename: Seon Ja
authors.initials: SJ
authors.lastname: Park
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Han
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000236:Adenoma / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000235:genetics*; D019175:DNA Methylation; D053843:DNA Mismatch Repair; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D013194:Staining and Labeling
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1