TY - JOUR
T1 - Altered topographic expression of p21(WAF1/CIP1/SDI1), bcl2 and p53 during gastric carcinogenesis
AU - Cho, Jeong Hee
AU - Kim, Woo Ho
N1 - Funding Information:
Acknowledgements. We sincerely appreciate the clinical supports of Dr. 1m Hwan Roe, Department of Internal Medicine and Dr. Min lung, Department of General Surgery. We also thank Dr. Mi Na Ha, Department of Epidemiology for statistical analysis and the proficient technical assistance of Mr. Sun Chul lang, Mr. lae Hwan Lee and Miss Hae Won Lee. This work was supported by the Dankook University 1996 Research Fund.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1998
Y1 - 1998
N2 - The accumulation of wild-type p53 protein results in two pathways, cell cycle G1 arrest by p21(WAF1/CIP1/SDI1) and apoptosis inhibited by bcl2, which together carry out the tumor suppressor function. Since genetic alterations of p53 are frequently observed in gastric cancers, the expression of p21 and bcl2 may be altered in gastric carcinogenesis. We therefore analyzed normal mucosa, nondysplastic lesions, hyperplastic polyps, adenomas and carcinomas of the human stomach using immunohistochemistry, polymerase chain reaction-single-strand conformation polymorphism and DNA sequencing. In normal gastric mucosa, the expression of p21, bcl2 and p53 was topographically restricted: a) p21 expression was limited to foveolar epithelial cells; b) bcl2 and p53 expression was confined to only a few regenerative epithelial cells of the mucous neck region. In chronic gastritis or intestinal metaplasia, topographic expression became more obvious. This topographic expression was altered in hyperplastic polyps and adenomas. Hyperplastic polyp showed an increased p21 and p53 expression with no bcl2 expression. Where as bcl2 expression increased and extended up parabasal and superficial dysplastic epithelium, p21 expression increased and was limited to surface dysplastic epithelium. Weak p53 expression was in full thickness of dysplastic epithelium. p21 and bcl2 expression in adenoma was higher than in intestinal type of carcinoma. In carcinomas, this topography was abrogated, but p53 mutation (36%) was present. There was no relationship between p53, p21 and bcl2 expression. As a result, in normal gastric epithelial cells, there was a precisely ordered topographic pattern of p21, bcl2 and wild-type p53 expression that becomes disordered during neoplasia. These results suggest that altered cell cycle and apoptosis control by wild-type p53 and its mediators appears to be an early event in gastric carcinogenesis that may facilitate tumor progression.
AB - The accumulation of wild-type p53 protein results in two pathways, cell cycle G1 arrest by p21(WAF1/CIP1/SDI1) and apoptosis inhibited by bcl2, which together carry out the tumor suppressor function. Since genetic alterations of p53 are frequently observed in gastric cancers, the expression of p21 and bcl2 may be altered in gastric carcinogenesis. We therefore analyzed normal mucosa, nondysplastic lesions, hyperplastic polyps, adenomas and carcinomas of the human stomach using immunohistochemistry, polymerase chain reaction-single-strand conformation polymorphism and DNA sequencing. In normal gastric mucosa, the expression of p21, bcl2 and p53 was topographically restricted: a) p21 expression was limited to foveolar epithelial cells; b) bcl2 and p53 expression was confined to only a few regenerative epithelial cells of the mucous neck region. In chronic gastritis or intestinal metaplasia, topographic expression became more obvious. This topographic expression was altered in hyperplastic polyps and adenomas. Hyperplastic polyp showed an increased p21 and p53 expression with no bcl2 expression. Where as bcl2 expression increased and extended up parabasal and superficial dysplastic epithelium, p21 expression increased and was limited to surface dysplastic epithelium. Weak p53 expression was in full thickness of dysplastic epithelium. p21 and bcl2 expression in adenoma was higher than in intestinal type of carcinoma. In carcinomas, this topography was abrogated, but p53 mutation (36%) was present. There was no relationship between p53, p21 and bcl2 expression. As a result, in normal gastric epithelial cells, there was a precisely ordered topographic pattern of p21, bcl2 and wild-type p53 expression that becomes disordered during neoplasia. These results suggest that altered cell cycle and apoptosis control by wild-type p53 and its mediators appears to be an early event in gastric carcinogenesis that may facilitate tumor progression.
KW - Direct DNA sequencing
KW - Gastric carcinogenesis
KW - Immunohistochemistry
KW - PCR-SSCP
KW - bcl2 and p53
KW - p21(WAF1/CIP1/SDI1)
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U2 - 10.1016/S0344-0338(98)80054-X
DO - 10.1016/S0344-0338(98)80054-X
M3 - Article
C2 - 9651943
AN - SCOPUS:0031841364
VL - 194
SP - 309
EP - 317
JO - Pathology Research and Practice
JF - Pathology Research and Practice
SN - 0344-0338
IS - 5
ER -
