EXPRESSION OF CYCLIN-DEPENDENT KINASE INHIBITOR P21(WAF1 CIP1) IN NONNEOPLASTIC MUCOSA AND NEOPLASIA OF THE STOMACH - RELATIONSHIP WITH P53STATUS AND PROLIFERATIVE ACTIVITY/

The expression of the p53-inducible cyclin-dependent kinase inhibitor p21(WAF1/CIP1) in non-neoplastic mucosa, adenoma, and adenocarcinoma o f the stomach was examined immunohistochemically and its relationship with p53 expression and proliferative activity was analysed, In normal gastric mucosa as well as in intestinal metaplasia the epithelial cel ls at the surface which showed no proliferative activity expressed p21 (WAF1/CIP1), whereas the cells in the deep area of the glands expressi ng Ki-67 did not, In the neoplastic lesions, the expression of p21(WAF 1/CIP1) was detected in 78 per cent (112/144) of the adenomas and 76 p er cent (262/343) of the adenocarcinomas, The incidence of p21(WAF1/CI P1) expression did not differ among histological types of gastric carc inoma, The strong expression of p21(WAF1/CIP1) was more frequently obs erved in carcinomas invading into submucosa or in cases of stages 2, 3 , and 4 than in carcinomas limited to the mucosa or in stage 1 cases, The incidence of strongly positive cases was higher in carcinomas with lymph node metastasis than in those without metastasis, There was no apparent correlation between the expression of p21(WAF1/CIP1) and the abnormal accumulation of p53 or with proliferative activity measured b y Ki-67 expression, These findings overall suggest that p21(WAF1/CIP1) might be associated with the senescence of non-neoplastic gastric epi thelial cells; that a p53-independent pathway might be substantially i nvolved in the induction of p21(WAF1/CIP1) in gastric neoplasia; and t hat the proliferative activity of gastric cancer might not be solely d ependent on control of the cell cycle by p21(WAF1/CIP1).