title: Distinct clinical features and outcomes of gastric cancers with microsatellite instability.
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.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Seung Im
authors.initials: SI
authors.lastname: Choi
authors.forename: Hyeon Kook
authors.initials: HK
authors.lastname: Lee
authors.forename: Hee Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Han-Kwang
authors.initials: HK
authors.lastname: Yang
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
authors.forename: Yong Il
authors.initials: YI
authors.lastname: Kim
authors.forename: Byung Lan
authors.initials: BL
authors.lastname: Lee
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002352:Carrier Proteins; D004268:DNA-Binding Proteins / Q000235:genetics; D050704:E2F4 Transcription Factor; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D000074081:MutS Homolog 3 Protein; D009363:Neoplasm Proteins / Q000032:analysis; D009367:Neoplasm Staging; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D017527:Receptor, IGF Type 2 / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics; D051028:bcl-2-Associated X Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C494826:BAX protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050704:E2F4 Transcription Factor; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; C078444:MSH3 protein, human; D000074081:MutS Homolog 3 Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017527:Receptor, IGF Type 2; D018125:Receptors, Transforming Growth Factor beta; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein