Microsatellite Instability In Precancerous Lesions And Gastric Cancer

Background: Gastric cancer(GC) is one of the most common malignant neoplasms among the world. Genetic alterations have been show to play roles in gastric carcinogenesis including abnormalities in proto-oncogenes, tumor suppressor genes, cell cycle regulator genes, tissue invasion-related genes, and mismatch repair genes. lintestinal metaplasia (IM) and dysplasia are considered precursor lesion of GC, but the genetic mechanism of early gastric carcinogenesis are not well knownObjective: To observe the changeable patterns of microsatellite instability (MSI) in GC and precancerous lesions, including IM and dysplasia. And to defermine the potential significance of MSI in the multistep gastric carcinogenesis pathway.Methods: We investigated MSI status in 30 flat dysplasias and 40 IMs without GC, and 30 GCs. Silver staining single strand conformation polymorphis polymerize chain reaction (PCR-SSCP) was used to screen 5 MSI markers , recommended by the National Cancer Institute, in formalin-fixed, paraffin-embeded tissues and corresponding normal gastric tissues. In this study, a high incidence of MSI (MSI-H) was defined as samplescontaining 30% or more MSI positive loci, a low incidence of MSI (MSI-L) as samples which had less than 30% loci instability, and MSS when samples displaying no alterations in 5 loci.Results: The abnormal shifting of the single-strand DNA was identified in 7 ( 23.3% ) out of GC, in 9 ( 30% ) out of dysplasia and in 8 ( 20% ) out of IM samples. Three ( 10% ) tumors, two ( 6.7% ) dysplasia and one ( 2.5% ) IM displayed MSI-H. MSI-L was detected in 13.3% of the tumors, in 23.3% dysplasia and in 17.5% IM samples. GC with MSI was associated with distal location of the tumors ( P=0.044 ), but no association was defined between MSI and age, gender, differentiation, lymph node metastasis and PTNM stage. Although MSI showed a trend for high-grade dysplasia, the differences were not significant. MSI was more likely observed in female with IM ( P=0.044 ) and in moderate-grade IM tissues ( 34.8% versus 0; P=0.013 ).Conclusions: The frequency of MSI in detected GC and precancerous lesions are almost the same when compared with previously reported data. MSI occurs not only in gastric adenomas and flat dysplasia coexisting with GC, but also in dysplasia without carcinoma. The progressive accumulation of MSI in areas of dysplasia and IM may contribute to GC development, suggesting that genetic instability may be an early somatic event of multistep gastric carcinogenesis.