Elsevier

Modern Pathology

Volume 15, Issue 6, 1 June 2002, Pages 632-640
Modern Pathology

Article
Distinct Clinical Features and Outcomes of Gastric Cancers with Microsatellite Instability

https://doi.org/10.1038/modpathol.3880578Get rights and content
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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.

Keywords

Gastric cancer
Microstellite instability
Survival analysis

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