Background & Aims: Microsatellite instability (MSI) in mitochondrial DNA (m
tDNA) is observed in some colorectal carcinomas. We attempted to determine
if mitochondrial MSI (mtMSI) and mutations occur in gastric carcinomas and
if the mtMSI phenotype underlies specific clinicopathologic profiles, Metho
ds: Sixty-two gastric carcinomas (34 intestinal and 28 diffuse types) were
investigated. Coding mutations in 8 different mitochondrial genes, mtMSI in
a noncoding (C)n tract, and p53 gene mutations were examined by polymerase
chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis
. MSI in nuclear DNA (nMSI) and loss of the p53 gene were examined using mi
crosatellite markers. Results: Ten of 62 (16%) carcinomas showed the mtMSI
phenotype. Mitochondrial gene mutation was detected in 5 carcinomas, 4 of w
hich also showed the mtMSI phenotype. There was a positive correlation betw
een mtMSI and nMSI status. In intestinal carcinomas, mtMSI, nMSI, and p53 g
ene alterations were frequently detected from early to advanced stages. In
diffuse carcinomas, both hinds of MSI were found in only advanced (subseros
al or serosal invasion) carcinomas. Six of 7 carcinomas with the nMSI pheno
type and all 5 carcinomas with mitochondrial coding mutations had a conside
rable intestinal-type tumor cell component. Conclusions: Mitochondrial gene
mutations, which are associated with the mtMSI phenotype, may play a speci
fic role in the tumorigenesis of intestinal-type gastric carcinomas.