Microsatellite analysis and DNA ploidy pattern in signet-ring cell carcinomas and well differentiated adenocarcinomas of the stomach

Background - Recently, numerous genetic abnormalities have been identified in gastric carcinomas. However, the crucial genetic event is still unclear. The aim of this study was to clarify the mechanisms of gastric carcinogene sis and progression, especially of signet-ring cell carcinomas (Sig,), by p erforming comparative studies with well differentiated adenocarcinomas (WD) . We examined loss of heterozygosity (LOHs) in the APC, p53, and E-cadherin genes and microsatellite. Methods - We examined loss of heterozygosity (LOHs) in the APC, p53, instab ility (MSI), as well as DNA ploidy alterations, in 25 Sig, and 20 WD. Results - In Sig., we found MSI in 16%, and LOHs in 16%, 12% and 24%, of th e APC, p53 and E-cadherin genes respectively. In WD, we found MSI in 25%, a nd LOHs in 25%, 40% and 10%, of the APC, p53 and E-cadherin genes respectiv ely. DNA aneuploidy was found in 32% of Sig., and In 65% of WD, Comparative studies revealed p53-LOH and DNA aneuploidy were more frequent in WD, and E-cadherin-LOH tended to he more frequent in Sig.. In total 45 carcinomas, all of which showed p53-LOH, were DNA aneuploid, and all MSI-positive carci nomas lacking p53-LOH were DNA diploid, Conclusions - These results suggest that gene abnormalities such as MSI and LOHs in the tumor suppression genes seem not to be frequent events in sign et-ring cell carcinomas, except for E-cadherin gene alterations. Furthermor e, MSI-positive carcinomas do not contain massive chromosome aberrations, i n contrast to the close correlation between p53-LOH and DNA aneuploidy in b oth subtypes of the gastric carcinomas.