Surgery Today

, Volume 35, Issue 12, pp 1005–1015 | Cite as

Microsatellite Instability in Gastrointestinal Tract Cancers: A Brief Update

  • Shinya Oda
  • Yan Zhao
  • Yoshihiko Maehara
Review Article


Microsatellite instability (MSI) was initially reported in colorectal cancer and, particularly, in hereditary nonpolyposis colorectal cancer (HNPCC). Since mutations in the genes functioning in DNA mismatch repair (MMR) were found in HNPCC kindred, this phenotype has been connected to a deficiency in MMR. The MSI+ phenotype is associated with various human malignancies. As MSI+ tumors appear to form a unique clinicopathological and molecular entity that is clearly distinct from that of classical colorectal tumors, which are accompanied by chromosomal instability (CIN), an exclusive pathway of tumorigenesis has been proposed in colorectal cancer. However, this scheme, comprising two mutually exclusive pathways, is now being reexamined, in light of a series of evidence accumulating in the literature, which relates to (a) distinction between high-level MSI (MSI-H) and low-level MSI (MSI-L), (b) heterogeneity in MSI-H, particularly in the sporadic and hereditary settings, (c) molecular mechanisms underlying the MSI+ phenotypes, and (d) relationships between the MSI+ and CIN phenotypes. Several molecular mechanisms may underlie repeat instability in eukaryotic cells. The relationship between MSI and defective MMR may be more complicated than has been suspected. The role of MMR deficiency in tumorigenesis in the digestive tract appears to be diverse and is not simple, even in the colorectum.

Key words

Replication error (RER) DNA mismatch repair hMSH2 hMLH1 


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Copyright information

© Springer-Verlag Tokyo 2005

Authors and Affiliations

  • Shinya Oda
    • 1
  • Yan Zhao
    • 1
    • 2
  • Yoshihiko Maehara
    • 2
  1. 1.Institute for Clinical ResearchNational Kyushu Cancer CenterFukuokaJapan
  2. 2.Department of Surgery and Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

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