Distinct clinical features and outcomes of gastric cancers with microsatellite instability

Hye Seung Lee, Seung Im Choi, Hyeon Kook Lee, Hee Sung Kim, Han Kwang Yang, Gyeong Hoon Kang, Yong I. Il Kim, Byung Lan Lee, Woo Ho Kim

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

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-β 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.

Original languageEnglish
Pages (from-to)632-640
Number of pages9
JournalModern Pathology
Volume15
Issue number6
DOIs
StatePublished - 2002

Keywords

  • Gastric cancer
  • Microstellite instability
  • Survival analysis

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