title: Comparison of clinicopathologic characteristics and genetic alterations between microsatellite instability-positive and microsatellite instability-negative sporadic colorectal carcinomas in patients younger than 40 years old.
abstract: OBJECTIVE
  Many studies have demonstrated that sporadic microsatellite instability-positive colorectal cancers share several clinicopathologic features with hereditary nonpolyposis colorectal cancers, including right-sided location, young age of onset, characteristic histomorphologic features, and a good prognosis. The aim of this study was to define distinct clinicopathologic features of sporadic microsatellite instability-positive colorectal cancers and to compare genotypic characteristics between microsatellite instability-positive and microsatellite instability-negative colorectal cancers in a young group.
  
  
  METHODS
  We analyzed 61 cases of young patients (<40 years old) with colorectal cancers for microsatellite instability at five mononucleotide and three dinucleotide repeats, loss of heterozygosity at APC and DCC, and K-ras and p53 mutations. Microsatellite instability status was correlated with molecular genetic factors and clinicopathologic parameters.
  
  
  RESULTS
  Microsatellite instability positivity was detected in 19 (31.1 percent) of 61 cases. Allelic alterations in TGFbetaRII, BAX, and IGFIIR were observed exclusively in microsatellite instability-positive tumors (63.1, 26.3, and 26.3 percent, respectively). Microsatellite instability-positive tumors exhibited a lower frequency of the p53 mutation (10.5 percent) than microsatellite instability-negative tumors (47.6 percent; P < 0.05). However, microsatellite instability status was not associated with APC or DCC allelic deletion or with the K-ras mutation. Microsatellite instability-positive colorectal cancers exhibited a proclivity toward proximal location, expansive growth pattern, and large tumor size (P < 0.05). Microsatellite instability-positive colorectal cancers had lower preoperative serum carcinoembryonic antigen levels (P < 0.05), a less advanced stage at presentation (P < 0.05), and a tendency toward better prognosis (P = 0.051) than microsatellite instability-negative colorectal cancers. However, there was no difference between microsatellite instability-positive and microsatellite instability-negative colorectal cancers regarding gross features, tumor grade, and extracellular mucin production.
  
  
  CONCLUSIONS
  These results suggest that sporadic microsatellite instability-positive colorectal cancers in young patients have different histomorphologic features from microsatellite instability-negative colorectal cancers and hereditary nonpolyposis colorectal cancers, some overlap of genetic alterations on multistep carcinogenesis with microsatellite instability-negative colorectal cancers, and a tendency for better prognosis.
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Suh
authors.forename: So-Dug
authors.initials: SD
authors.lastname: Lim
authors.forename: Jin Cheon
authors.initials: JC
authors.lastname: Kim
authors.forename: Sook Hee
authors.initials: SH
authors.lastname: Hong
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D017491:Genes, APC; D016163:Genes, DCC; D016158:Genes, p53; D011905:Genes, ras; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation