Clonal analysis of gastric carcinoma and precancerous lesions and its relation to Ki-67 protein expression

The pathogenesis of intestinal carcinoma is characterized as progressing through multiple steps, which begin with atrophic gastritis followed by intestinal metaplasia, dysplasia and carcinoma. However, the clonal status of gastric precancerous lesions and its association with proliferative kinetics have not been fully understood. In this study, gastric lesions and normal epithelial cells were isolated from formalin-fixed paraffin embedded tissues using a laser capture microdissection (LCM) system, the clonality was analyzed with human androgen receptor gene (HUMARA) polymerase chain reaction (PCR), and the PCR products were examined using Applied Biosystems 3730 DNA Analyzer. The relationship between the clonal status and Ki-67 protein expression was also investigated. Ki-67 was detected by two-step immunohistochemical staining. 5/32 intestinal metaplasia lesions, 10/45 low grade intraepithelial neoplasia, 25/36 high grade intraepithelial neoplasia and 20/20 intestinal gastric carcinoma were of monoclonal origin. Similar to monoclonal inactivation, the expression rate of Ki-67 also increased along the multi-step gastric carcinogenesis. Clonal status was associated with the expression rate of Ki-67 to a certain extent, which may be useful in assessing susceptibility to gastric carcinoma. Key words: gastric carcinoma; precancerous lesion; clonal analysis; Ki-67.