High-resolution fluorescent analysis of microsatellite instability in gastric cancer

Abstract

Background: Microsatellite instability (MSI) is associated with various human malignancies and regarded as reflecting cellular deficiency in DNA mismatch repair (MMR). Analysis of MSI has been prevalent in the field of oncology, and numerous data have accumulated in the literature. It has been reported that the MSI+ phenotype is relatively frequent in gastric cancer. The reported frequencies of MSI+ gastric tumors, however, are diverse.

Aim and methods: To determine the frequencies of the MSI+ phenotype and defective MMR in gastric cancer, we examined tumors derived from 167 patients with sporadic gastric cancer, using our unique fluorescent technique, 'high-resolution fluorescent microsatellite analysis'.

Results: High-resolution fluorescent microsatellite analysis allowed us the unequivocal designation of MSI. The frequencies of MSI-H and MSI-L were 11 and 9.6%, respectively. In addition to the distinction based on the frequency of microsatellite changes, MSI was classifiable into two distinct categories, type A and type B, according to the mode of length changes in the dinucleotide microsatellites. Type A and type B MSI were observed in 14 and 6.6%, respectively. The overall frequency of MSI was 21%. Intriguingly, MSI did not correlate with any of commonly used clinicopathological variables. In addition, neither MSI-H nor MSI-L correlated with family history of malignancies or patient history of multiple cancers. Instead, type B MSI was significantly more frequent in patients with family history of gastric cancer. Type A MSI appeared to occur more frequently in tumors of patients with a history of double cancer, which, however, was not statistically significant.

Conclusion: In gastric cancer, contribution of defective MMR to the risk of multiple cancer or familial predisposition appears more limited than has been expected. The relationship between MSI and high risk of cancer may have been oversimplified, at least in gastric cancer.