Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In general, colorectal carcinoma is thought to originate mainly from adenoma, and this pathway is called the adenoma-carcinoma sequence. Carcinoma in adenoma is an appropriate model for analysis of this mechanism, because adenoma and carcinoma tissues coexist in the same polyp and the carcinoma is thought to have originated from the surrounding adenoma. Expression of the p53 protein was analyzed in 36 cases of carcinoma in adenoma in the colon by immunohistochemistry using an anti-human p53 monoclonal antibody (PAb1801). Alterations of the p53 gene were analyzed by the polymerase chain reaction for microanalysis of normal mucosa, adenoma, and carcinoma from histological slides. Mutations were assessed by the polymerase chain reaction-single strand conformation polymorphism analysis and identified by DNA sequencing in some cases. Loss of heterozygosity was studied by polymerase chain reaction-restriction fragment length polymorphism analysis. Positive staining for p53 was detected in three (8%) of 37 adenomas and 20 (53%) of 38 focal carcinomas. One (7%) of 15 adenomas with mild dysplasia, three (14%) of 22 adenomas with moderate dysplasia, and 16 (42%) of 38 focal carcinomas had a mutation in exon 5 through exon 8 of the p53 gene. As for allelic loss in the p53 gene locus, only one adenoma with moderate dysplasia had loss of heterozygosity, whereas six (40%) of 15 focal carcinomas had loss of heterozygosity. Of those tumors (3 of 37 adenomas and 20 of 38 focal carcinomas) that reacted with PAb1801, 78% (18 of 23) showed genetic alterations. Among 52 tumors which showed negative staining, five tumors had a p53 mutation and four of them were nonsense mutations. Putting all of these results together, 71% (24 of 34) of the cases underwent p53 gene and protein alterations during the conversion from adenoma to focal carcinoma. These data clearly indicate that genetic alterations of p53 are involved mainly in the malignant transformation from adenoma to focal carcinoma in colon carcinogenesis. In addition, some cases show heterogeneity of the p53 gene in carcinoma in adenoma of the colon. There may be other pathways than p53 responsible for malignant change in the colon.
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PMID:A frequent alteration of p53 gene in carcinoma in adenoma of colon. 806 81

Twenty-six specimens of tubular adenoma and 7 specimens of adenocarcinoma in adenoma of the colon were examined to evaluate apoptosis between adenoma and early adenocarcinoma. Cell proliferation and cell death seemed to be balanced in adenoma with mild and moderate atypia, but unbalanced in adenoma with severe atypia and cancer. Apoptosis was considered to be suppressed at cancer in some cases. However, a number of apoptosis increased at cancer in other cases. Necrosis was seen only in cancer areas. The ratio of cells simultaneously stained by anti-Ki-67 antibody (MIB-1) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling (TUNEL) tended to be high from adenoma with moderate atypia to cancer, suggesting the unstableness of DNA. It is possible that cancer cells having highly unstable DNA easily underwent apoptosis as well as necrosis, accidentally. The p53 protein was positive only in cancer areas of three cases. One of these three showed decreased apoptosis in a cancer area, but the other two cases showed increased apoptosis. Furthermore, certain numbers of cancer cells were double-stained by p53 immunohistochemistry and TUNEL. These results suggest that the p53 protein may contribute to suppress apoptosis in the last stage of carcinogenesis of the colonic adenocarcinoma, but other factors including extrinsic stimulation may cause apoptosis despite the mutation of p53 protein.
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PMID:Apoptosis in adenoma and early adenocarcinoma of the colon. 969 Jan 32

We present a case of intra-epithelial carcinoma occurring in a serrated adenoma of the colon. The pedunculated polyp, which measured 12 x 10 x 6 mm, was endoscopically removed from the ascending colon of a 78-year-old woman. Histologically, the polyp mainly consisted of serrated adenomatous glands, and had foci of intra-epithelial carcinoma at the top. Hyperplastic (metaplastic) areas were also present in both borders between the serrated adenomatous area and the surrounding normal mucosa. A sequential increase in the degree of dysplasia, and in the number of nuclei positively reactive for Ki-67 and p53 was evident from the hyperplastic areas toward the foci of carcinoma. The polyp described here may represent a carcinogenic potential of hyperplastic polyp via serrated adenoma.
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PMID:Colonic intra-epithelial carcinoma occurring in a hyperplastic polyp via a serrated adenoma. 1132 39