title: High-fidelity of five quasimonomorphic mononucleotide repeats to high-frequency microsatellite instability distribution in early-stage adenocarcinoma of the colon.
abstract: BACKGROUND
  Microsatellite instability (MSI) in colorectal cancer (CRC) is a distinct pathway of carcinogenesis with prognostic implications. MSI is identified through the use of several markers. The aim of this study was to test the fidelity of five markers for high-frequency MSI (MSI-H) across age groups and stages.
  
  
  METHODS
  Analysis of the fidelity of five mononucleotide markers to MSI-H and the prevalence of MSI in different parts of the colon was carried out using BAT-26, BAT-25, NR-24, NR-21 and NR-27 in a cohort of predominantly Norwegian patients with stage I-III colon cancer.
  
  
  RESULTS
  Of the 121 colon tumors, a total of 33 (27.3%) were MSI-H, only 3 (2.5%) were low-frequency MSI and the rest (n=85, 70.2%) were microsatellite stable. The fidelity for MSI-H (n=33) of each marker was very high, with 100% for BAT-26, 96.9% for BAT-25, 87.5% for NR-24, 97.0% for NR-21, and 97% for NR-27. MSI prevalence was much higher in the proximal compared to the distal colon (43.1% vs. 8.9%; p<0.001). The prevalence of MSI-H decreased with increasing age, from >55% in those <50 years to 21% in those >70 years of age. For early-stage colon cancer (stage I-II, n=83), there was a significant difference in MSI distribution (44% in those <60 years and 22% in those >60 years; p=0.047), and in proximal (52.2%) compared to distal (7%) location (p<0.001). Highest prevalence (75%) of MSI-H was found in the proximal colon of node-negative patients <60 years of age.
  
  
  CONCLUSIONS
  The five quasimonomorphic mononucleotide markers demonstrated high fidelity for MSI-H, with few cases being low frequency. MSI-H was most prevalent in early-stage, proximal colon cancer and in those <60 years, which may have implications for molecular screening.
authors.affiliation: Department of Surgery, Stavanger University Hospital, Armauer Hansensvei 20, POB 8100, N-4068 Stavanger, Norway. ksoreide@mac.com
authors.forename: Kjetil
authors.initials: K
authors.lastname: Søreide
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D017677:Age Distribution; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D053842:Microsatellite Instability; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D009711:Nucleotides / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D009711:Nucleotides