Original Article
Mod Pathol 2002;15(6):632–640
Distinct Clinical Features and Outcomes of Gastric Cancers with Microsatellite Instability
Hye Seung Lee M.D.1, Seung Im Choi M.S.1, Hyeon Kook Lee M.D.2, Hee Sung Kim M.D.4, Han-Kwang Yang M.D.2, Gyeong Hoon Kang M.D.1, Yong Il Kim M.D.1, Byung Lan Lee M.D.3 and Woo Ho Kim M.D.1,3
- 1Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
- 2Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- 3Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
- 4Department of Pathology, National Cancer Center, Gyeonggi-do, Korea
Correspondence: 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: woohokim@snu.ac.kr; fax: 82-2-765-5600
Accepted 12 March 2002.
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-
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
