Analysis of microsatellite instability, protein expression and methylation status of hMLH1 and hMSH2 genes in gastric carcinomas

Microsatellite instability (MSI) is a manifestation of a defective DNA mismatch repair system. It is caused by germline mutations of mismatch repair genes or CpG islands hypermethylation. The majority of cancers of hereditary nonpolyposis colorectal cancer (HNPCC) syndrome have MSI+ phenotype. The c...

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Published inHepato-gastroenterology Vol. 56; no. 91-92; p. 899
Main Authors Gu, Mijin, Kim, DongSun, Bae, YoungKyung, Choi, JoonHyuk, Kim, SangWoon, Song, SunKyo
Format Journal Article
LanguageEnglish
Published Greece 01.05.2009
Subjects
Adaptor Proteins, Signal Transducing - physiology
Adult
Aged
Aged, 80 and over
Carcinoma - genetics
Carcinoma - metabolism
Carcinoma - pathology
Cohort Studies
Female
Humans
Male
Microsatellite Instability
Middle Aged
MutL Protein Homolog 1
MutS Homolog 2 Protein - physiology
Neoplasm Invasiveness
Nuclear Proteins - physiology
Retrospective Studies
Sensitivity and Specificity
Stomach Neoplasms - genetics
Stomach Neoplasms - metabolism
Stomach Neoplasms - pathology
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Summary:Microsatellite instability (MSI) is a manifestation of a defective DNA mismatch repair system. It is caused by germline mutations of mismatch repair genes or CpG islands hypermethylation. The majority of cancers of hereditary nonpolyposis colorectal cancer (HNPCC) syndrome have MSI+ phenotype. The colorectal cancers show distinctive clinicopathological characteristics and prognoses according to the MSI status. However, there is a wide variety of results between MSI and clinicopathological parameters in gastric carcinomas. Five hundred and twenty-one surgically resected gastric carcinomas were studied and the correlation with clinicopathological parameters, MSI status by using five microsatellite markers, expression of hMLH1 and hMSH2 protein by immunohistochemical stain, and methylation of hMLH1 and hMSH2 by methylation-specific polymerase chain reaction was analyzed. There were 50 (9.6%) high-frequency MSI (MSI-H) cases. The MSI-H gastric carcinomas were associated with older age, expanding type by Ming's classification, lymphatic invasion, tumor multiplicity, losses of hMLH1 and hMSH2 protein expressions. The methylation frequency of hMLH1 was 75.5% in MSI-H gastric carcinomas. Our results suggest that epigenetic inactivation of hMLH1 might play a role in the carcinogenesis of MSI-H gastric carcinomas. The immunohistochemical stain for hMLH1 protein expression could be used in routine diagnostic methods for predicting MSI status.
ISSN:0172-6390