OBJECTIVETo study the clonality of gastric carcinoma and precancerous lesions and its relationship with Ki-67 protein expression.

METHODSFormalin-fixed paraffin embedded tissues were collected from 174 cases of gastric endoscopic biopsies and surgical removed specimens. The lesional tissues were isolated by Laser Capture Microdissection. Methylation sensitive restriction enzyme (HpaII) digestion and polymerase chain reaction (PCR) were used to detect the clonality at the polymorphic human androgen receptor gene locus on the X chromosome. PCR products were analyzed by capillary electrophoresis using applied Biosystems 3730 DNA Analyzer. In addition, a two-step immunohistochemical staining EnVision method was used to detect the expression of Ki-67 protein.

RESULTSThe frequency of detection of monoclonality and expression rate of Ki-67 were found increased in a stepwise fashion from gastrointestinal metaplasia, low grade intraepithelial neoplasia, high grade intraepithelial neoplasia to intestinal carcinoma (15.63%, 5/32; 22.22%, 10/45; 69.44%, 25/36 and 100.0%, 20/20; respectively). The presence of clonal proliferation was correlated with Ki-67 expression in low grade intraepithelial neoplasia (P < 0.01).

CONCLUSIONSThe presence of clonal proliferation and increased Ki-67 are increasingly detected in the lesions along the multi-step gastric carcinogenesis model. Clonal status is associated with the expression rate of Ki-67 to a certain extent, suggesting a combined application of both markers may be useful in assessing early stages of gastric carcinoma.