TP53 and gastric carcinoma: a review.
In this article, we survey the major p53 (TP53) alterations identified in gastric carcinomas and their precursors. These include p53 expression, mutations, and loss of heterozygosity (LOH). Not only are the various abnormalities summarized, but in addition there is a survey of the literature with respect to the impact of these changes on patient prognosis and treatment response. The majority of published studies involve the immunohistochemical detection of the protein. These use different antibodies, different detection techniques, and different methods of interpretation. Therefore not surprisingly, the results of many of the studies are contradictory with one another. Overall, however, it appears that p53 alterations occur early in the development of gastric carcinoma, being present even in the nonneoplastic mucosa and they increase in frequency as one progresses along the pathway of gastric carcinoma development. p53 immunoreactivity is seen in 17%-90.7% of invasive gastric carcinomas. p53 alterations occur much more commonly in proximal lesions than in distal ones, suggesting that the molecular events leading to the development of gastric carcinoma may be very different in proximal vs. distal tumors. p53 mutations occur in 0%-77% of gastric carcinomas. The mutations are distributed widely across the gene from exons 4-11 with hot spots of mutation at codons 175, 248, 273, 282, 245, and 213. G:C>A:T transitions at CpG sites are the commonest type of mutation. At least 60% of carcinomas with mutations also exhibit p53 LOH.
Fenoglio-Preiser
C M
CM
Department of Pathology, College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0529, USA. Cecilia.FenoglioPreiser@UC.Edu
Wang
J
J
Stemmermann
G N
GN
Noffsinger
A
A
D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation; D013274:Stomach Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53