p53, But not c-Ki-ras, mutation and down-regulation of p21(WAF1/CIP1) and cyclin D1 are associated with malignant transformation in gastric hyperplastic polyps

To investigate tumorigenesis in th gastric hyperplastic polyp (HP), we eval uated 19 HPs with and 50 HPs without dysplasia (including carcinoma in situ ), as compared with normal mucosa and fundic gland polyps. Helicobacter pyl ori density was highest in HPs without dysplasia. Apoptotic activity and Ki -67 and p53 expression also were higher in dysplasia in HPs than in normal mucosa, fundic gland polyps, or HPs themselves. The p21(WAFI)/(CIP1) and cy clin D1 levels, in contrast, were:highest in HPs. In HPs without dysplasia, size was correlated positively with the degree of stromal inflammation and with p53 and cyclin DI expression. p53 and c-Ki-ras mutations were defecte d in 41% (8/19) and 5% (1/19) of dysplasia (including carcinoma insitu) in HPs. Our results demonstrate that the HP enlarges with enhanced cell turnov er and overexpression of p53, p21(WAFI/CIP1), and cyclin D1, associated wit h H pylori-related inflammation, and that p53 but not c-Ki-ras mutations ma y have an important role in dysplastic change in HPs.