Microsatellite instability, prognosis and metastasis in gastric cancers from a low-risk population

Int J Cancer. 2000 Sep 20;89(5):444-52. doi: 10.1002/1097-0215(20000920)89:5<444::aid-ijc8>3.0.co;2-f.

Abstract

We examined 169 cases of gastric adenocarcinoma for microsatellite instability (MSI), using a panel of 8 microsatellite markers. Of these cases, 142 were from the United States, a country of relatively low risk for gastric cancer. Comparing microdissected tumors to normal cells from the same patient, we classified tumors as being microsatellite-stable (MSS) or having a low frequency of MSI (MSI-L, up to 30% of markers different in the tumor) or a high frequency of MSI (MSI-H, 30% or more of markers different). Among our American cases, we identified 26 (18.2%) showing MSI-H and 15 (10.6%) showing MSI-L. Twenty cases were from Korean patients, and they showed no significant differences in proportions of MSI-H and MSI-L from the American cases. MSI-H tumors in the American patients were characterized by elevated frequencies of band shifts in repeat sequences of the BAX (50%), transforming growth factor-beta receptor type II (TGFbetaRII, 68.9%), beta(2)-microglobulin (21.4%) and E2F4 (51.7%) genes. Alterations in E2F4 in MSI-H tumors were always integral multiples of 3 nucleotides lost or gained, which would not cause a frameshift mutation, and within the range of normal polymorphisms for this sequence. North American patients (n = 127) with MSI-H and MSI-L tumors had a longer median survival of 541 days and 587 days, respectively, compared to 265 days for patients with MSS tumors (p = 0.027). This survival difference may result from a significantly greater tendency for metastases in the MSS group (p = 0.031).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Humans
  • Microsatellite Repeats*
  • Neoplasm Metastasis
  • Prognosis
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2*
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Survival Rate
  • bcl-2-Associated X Protein
  • beta 2-Microglobulin / genetics

Substances

  • BAX protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Transforming Growth Factor beta
  • bcl-2-Associated X Protein
  • beta 2-Microglobulin
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II