Genetic alterations of sporadic colorectal cancer with microsatellite instability, especially characteristics of primary multiple colorectal cancers

J Surg Oncol. 2000 Aug;74(4):249-56. doi: 10.1002/1096-9098(200008)74:4<249::aid-jso2>;2-s.


Background and objectives: The purpose of this study was to elucidate genetic alterations of sporadic colorectal cancers with Microsatellite instability (MSI).

Methods: One hundred and ten patients with sporadic colorectal cancer were examined. The MSI was assessed using eight microsatellite markers. In addition, mutation analysis was performed for Transforming growth-beta type II receptor (TGF beta R II), bcl-2 associated X protein (BAX), Insulin-like growth factor II receptor (IGF II R), human MutS homolog 3 (hMSH3), human MutS homolog 6 (hMSH6), human MutS homolog 2 (hMSH2), and human MutL homolog 1 (hMLH1) genes. Tumors with three or more positive loci have been determined to be MSI-H (high-frequency MSI), tumors with one or two positive loci were designated as MSI-L (low-frequency MSI) and tumors lacking apparent instability were designated as MSS (microsatellite stable).

Results: There were 11 cases with MSI-H (MSI-H group) and 99 cases with MSI-L/MSS (MSI-L/MSS group). The frequency of cases with multiple colorectal cancer in the MSI-H group was significantly higher than that of MSI-L and MSS group (81.8% vs. 34.3%, p = 0.0022). The frequency of cases with multiple cancers increased as the number of locus with microsatellite instability increased. Among 11 tumors with MSI-H, 7 indicated mutation of the TGF beta R II (63.6%), whereas no tumor had a mutation of the TGF beta R II among 20 tumors with MSI-L (p = 0.0001). Regarding the BAX, hMSH3, hMSH6 gene, the same trend was obtained as the TGF beta R II gene (18.2% vs. 0%, p = 0.0487, 36.4% vs. 0%, p = 0.0039, 27.3% vs. 0%, p = 0.0140, respectively). Only two cases indicated a somatic point mutation of the hMSH2 gene.

Conclusions: The multiple occurrence of the colorectal carcinoma may be related to MSI-H as well as the mutation of genes possessing repetitive mononucleotide tracts. Furthermore, we recommend strict follow-up in sporadic colorectal patients that indicate MSI-H.

Publication types

  • Comparative Study

MeSH terms

  • Base Sequence
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics*
  • DNA Mutational Analysis
  • DNA, Neoplasm / analysis
  • Female
  • Genetic Markers
  • Humans
  • Male
  • Microsatellite Repeats*
  • Molecular Sequence Data
  • Mutation / genetics*
  • Neoplasms, Multiple Primary / epidemiology
  • Neoplasms, Multiple Primary / genetics*
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational*
  • Sensitivity and Specificity


  • DNA, Neoplasm
  • Genetic Markers