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EXPRESSION OF CYCLIN‐DEPENDENT KINASE INHIBITOR p21 WAF1/CIP1 IN NON‐NEOPLASTIC MUCOSA AND NEOPLASIA OF THE STOMACH: RELATIONSHIP WITH p53 STATUS AND PROLIFERATIVE ACTIVITY
Author(s) -
YASUI WATARU,
AKAMA YOSHIHIKO,
KUNIYASU HIROKI,
YOKOZAKI HIROSHI,
SEMBA SHUHO,
SHIMAMOTO FUMIO,
TAHARA EIICHI
Publication year - 1996
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199610)180:2<122::aid-path647>3.0.co;2-c
Subject(s) - cancer research , biology , cyclin d , kinase , cyclin , stomach , cyclin d1 , cyclin dependent kinase 4 , microbiology and biotechnology , pathology , cell cycle , cyclin dependent kinase 2 , medicine , cell , protein kinase a , genetics , biochemistry
The expression of the p53‐inducible cyclin‐dependent kinase inhibitor p21 WAF1/CIP1 in non‐neoplastic mucosa, adenoma, and adenocarcinoma of 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 cells at the surface which showed no proliferative activity expressed p21whereas the cells in the deep area of the glands expressing Ki‐67 did not. In the neoplastic lesions, the expression of p21 WAF1/CIP1 was detected in 78 per cent (112/144) of the adenomas and 76 per cent (262/343) of the adenocarcinomas. The incidence of p21 WAF1/CIP1 expression did not differ among histological types of gastric carcinoma. The strong expression of p21 WAF1/CIP1 was more frequently observed 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 by Ki‐67 expression. These findings overall suggest that p21 WAF1/CIP1 might be associated with the senescence of non‐neoplastic gastric epithelial cells; that a p53‐independent pathway might be substantially involved in the induction of p21 WAF1/CIP1 in gastric neoplasia; and that the proliferative activity of gastric cancer might not be solely dependent on control of the cell cycle by p21 WAF1/CIP1 .