Mitochondrial microsatellite instability in gastric cancer and gastric epithelial dysplasia as a precancerous lesion

Abstract

Background: Genetic instability in gastric cancer represents a key molecular step that occurs early in the carcinogenesis process. To clarify the role of genetic instability in the progression from gastric dysplasia to gastric cancer, mitochondrial microsatellite instability (mtMSI) was studied in gastric cancer and gastric dysplasia. Methods: DNA was isolated from paired normal and tumoral tissues in 24 patients with gastric dysplasia (low grade) and 49 patients with gastric cancer. mtMSI was analyzed using eight microsatellite markers. mtMSI in gastric dysplasia was studied prospectively to elucidate the relation between mtMSI and gastric carcinogenesis. Results: mtMSI was found in 5 (10.2%) of 49 gastric cancer patients. The mtMSI phenotype was not associated with age, gender, and Helicobacter pylori infection. However, all of the mtMSI was found in intestinal-type gastric cancer (20.8%, p = 0.02). In gastric dysplasia, mtMSI was detected in 3 (12.5%) of 24 patients with gastric dysplasia. mtMSI-positive gastric dysplasia showed a poor prognosis statistically compared to mtMSI negative through progression to high-grade dysplasia or gastric cancer. Conclusions: These data suggest that mtMSI may be an early and important event in the progression of gastric carcinogenesis, especially in intestinal-type gastric cancer.

Abbreviations ATP, adenosine-5′-triphosphate; COI, cytochrome oxidase subunit 1; mtDNA, mitochondrial DNA; mtMSI, mitochondrial microsatellite instability; nMSI, nuclear microsatellite instability; OXPHOS, oxidative phosphorylation; ROS, reactive oxygen species Keywords Gastric cancer; Gastric dysplasia; Genetic instability; Mitochondrial microsatellite instability