Distinct clinical features and outcomes of gastric cancers with microsatellite instability

Mod Pathol. 2002 Jun;15(6):632-40. doi: 10.1038/modpathol.3880578.

Abstract

Microsatellite instability (MSI) is a hallmark of the DNA mismatch repair deficiency that is one of the pathways of gastric carcinogenesis. Clinicopathologic characteristics of MSI+ gastric cancers remain unclear. To determine the correlation between MSI status and clinical features, we analyzed 327 consecutive gastric cancers for the occurrence of MSI in the BAT-26 marker. Because it has been proven that MSI at BAT-26 reflects the MSI+ phenotype, cancers with alteration at BAT-26 were categorized as having the MSI+ phenotype. The expressions of hMLH1, hMSH2, p53, MUC1, MUC2, and CEA were evaluated immunohistochemically using the tissue array method. The MSI+ phenotype was found in 9.5% (31/327) of gastric cancers examined. MSI+ gastric cancers were significantly associated with older age, antral location, Borrmann's gross Type II, intestinal subtype, lower prevalence of lymph node metastasis, and lower pTNM stage (P <.05). By multivariate logistic regression, MSI+ gastric cancers had a lower prevalence of lymph node metastasis independent of tumor invasion (P <.001). MSI+ gastric cancers displayed frequent frameshift mutations of transforming growth factor-beta type II receptor (90.3%), BAX (61.3%), hMSH3 (38.7%), and E2F4 (61.3%) genes and diminished hMLH1 (24/31) or hMSH2 (4/31) expressions. The MSI+ phenotype correlated with patient survival in advanced gastric carcinoma (P =.046). In conclusion, MSI+ phenotype in gastric cancers was found to have distinct clinicopathologic characteristics and to be predictive of a favorable outcome in advanced carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Analysis of Variance
  • Carrier Proteins
  • DNA-Binding Proteins / genetics
  • E2F4 Transcription Factor
  • Female
  • Frameshift Mutation
  • Humans
  • Immunohistochemistry
  • Male
  • Microsatellite Repeats / genetics*
  • Middle Aged
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • MutS Homolog 3 Protein
  • Neoplasm Proteins / analysis
  • Neoplasm Staging
  • Nuclear Proteins
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2*
  • Receptor, IGF Type 2 / genetics
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Survival Analysis
  • Transcription Factors / genetics
  • bcl-2-Associated X Protein

Substances

  • Adaptor Proteins, Signal Transducing
  • BAX protein, human
  • Carrier Proteins
  • DNA-Binding Proteins
  • E2F4 Transcription Factor
  • G-T mismatch-binding protein
  • MLH1 protein, human
  • MSH3 protein, human
  • MutS Homolog 3 Protein
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptor, IGF Type 2
  • Receptors, Transforming Growth Factor beta
  • Transcription Factors
  • bcl-2-Associated X Protein
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein