p53, but not c-Ki-ras, mutation and down-regulation of p21WAF1/CIP1 and cyclin D1 are associated with malignant transformation in gastric hyperplastic polyps.
To investigate tumorigenesis in the gastric hyperplastic polyp (HP), we evaluated 19 HPs with and 50 HPs without dysplasia (including carcinoma in situ), as compared with normal mucosa and fundic gland polyps. Helicobacter pylori 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 p21WAF1/CIP1 and cyclin 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 D1 expression. p53 and c-Ki-ras mutations were detected in 41% (8/19) and 5% (1/19) of dysplasia (including carcinoma in situ) in HPs. Our results demonstrate that the HP enlarges with enhanced cell turnover and overexpression of p53, p21WAF1/CIP1, and cyclin D1, associated with H pylori-related inflammation, and that p53 but not c-Ki-ras mutations may have an important role in dysplastic change in HPs.
Murakami
K
K
Departments of Internal Medicine, School of Medicine, Kitasato University, Sagamihara, Japan.
Mitomi
H
H
Yamashita
K
K
Tanabe
S
S
Saigenji
K
K
Okayasu
I
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D019938:Cyclin D1 / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000032:analysis; D015536:Down-Regulation; D005260:Female; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011127:Polyps / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D016283:Proto-Oncogene Proteins p21(ras)