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.
Bibliographical noteFunding Information:
Copyright © 2002 by The United States and Canadian Academy of Pathology, Inc. VOL. 15, NO. 6, P. 632, 2002 Printed in the U.S.A. Date of acceptance: March 12, 2002. This study was supported by the 21C Frontier Functional Human Genome Project of the Ministry of Science and Technology of Korea. Address reprint requests to: Woo Ho Kim, M.D., Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Korea; e-mail: firstname.lastname@example.org; fax: 82-2-765-5600.
- Gastric cancer
- Microstellite instability
- Survival analysis