Microsatellite instability in synchronous gastric carcinomas.
Synchronous gastric carcinomas are found in 4% to 10% of all gastric carcinomas, and the tumor multiplicity is believed to be related to genetic predisposition. To investigate the role of mismatch repair error in synchronous gastric carcinomas, we analyzed the microsatellite instability (MSI) status of 101 cancers from 48 gastrectomy specimens and compared them with 149 solitary gastric carcinomas. Multiple synchronous gastric carcinomas are characterized by slightly older age, predominance in males, early stage and lower lymph node metastasis. Among the 48 cases, 8 (18 lesions) were associated with a gastric adenoma (type I) and 40 (83 lesions) were not associated with a gastric adenoma (type II). The MSI+ rate was 50% in the type I and 8.4% in the type II synchronous gastric carcinomas (p < 0.001), while that of solitary gastric carcinomas was 9.4%. In addition, the frameshift mutation rates of the TGF-betaRII, BAX and hMSH3 genes in the type I synchronous carcinomas were higher than those in the type II synchronous carcinomas. These findings indicate that a defect in the mismatch repair system might play a role in the carcinogenesis of a minor subset of multiple gastric carcinomas associated with adenomas.
Lee
H S
HS
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
Lee
B L
BL
Kim
S H
SH
Woo
D K
DK
Kim
H S
HS
Kim
W H
WH
D048868:Adaptor Proteins, Signal Transducing; D000236:Adenoma / Q000235:genetics; D000367:Age Factors; D000368:Aged; D000483:Alleles; D020137:Base Pair Mismatch; D002277:Carcinoma / Q000235:genetics*; D002352:Carrier Proteins; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D000074081:MutS Homolog 3 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009378:Neoplasms, Multiple Primary / Q000235:genetics; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion; D051028:bcl-2-Associated X Protein
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D000074081:MutS Homolog 3 Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C501486:MLH1 protein, human; C078444:MSH3 protein, human; C497172:MSH2 protein, human; C421109:multidrug resistance-associated protein 1