Gastric carcinomas with microsatellite instability: clinical features and mutations to the TGF-beta type II receptor, IGFII receptor, and BAX genes

J Pathol. 1999 Mar;187(4):428-32. doi: 10.1002/(SICI)1096-9896(199903)187:4<428::AID-PATH264>3.0.CO;2-A.


The replication error phenotype (RER+) represents an important new form of genetic alteration characterized by widespread instability in repetitive nucleotide sequences. The aim of this study was to compare the features of RER+ gastric tumours with those of RER+ colonic tumours. RER status was determined by analysis of size alterations in the BAT-26 mononucleotide repeat microsatellite. Twelve of 121 (10 per cent) gastric carcinomas from a low-incidence region were found to be RER+. BAT-26 instability was associated with tumours showing an absence of nodal invasion ( p=0.009) and with a trend for improved prognosis. These tumours were more frequent in older, female patients. Frameshift mutations in mononucleotide repeat sequences within the transforming growth factor-beta receptor II (RII), insulin-like growth factor II receptor (IGFIIR), and BAX genes were observed in 83, 33, and 25 per cent, respectively, of RER+ tumours. Only 1/12 (8 per cent) RER+ tumours contained a p53 gene mutation compared with 29/109 (27 per cent) RER- tumours. RER+ gastric carcinomas therefore share several important features with RER+ colonic tumours, including less frequent nodal invasion, improved prognosis, a similar frequency of mutation in growth control genes containing repetitive nucleotide sequences, and a low frequency of mutation of the p53 tumour suppressor gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Female
  • Humans
  • Male
  • Microsatellite Repeats*
  • Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2*
  • Receptor, IGF Type 2 / genetics
  • Receptors, Transforming Growth Factor beta / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • bcl-2-Associated X Protein


  • BAX protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptor, IGF Type 2
  • Receptors, Transforming Growth Factor beta
  • bcl-2-Associated X Protein