Multiple hyperplastic polyps in the stomach: Evidence for clonality and neoplastic potential

Autor: S.M.M. Dijkhuizen, M.M. Entius, Marjon J. Clement, M. E. Craanen, G. J. A. Offerhaus, F. M. Van Den Berg, M. M. Polak, Robbert J.C. Slebos
Přispěvatelé: Faculteit der Geneeskunde, Other departments, VU University medical center
Rok vydání: 1997
Předmět:
Zdroj: Gastroenterology, 112, 561-566. W.B. Saunders Ltd
Dijkhuizen, S M M, Entius, M M, Clement, M J, van den Berg, F M, Polak, M M, Craanen, M E, Slebos, R J C & Offerhaus, G J A 1997, ' Multiple hyperplastic polyps in the stomach: evidence for clonality and neoplastic potential ', Gastroenterology, vol. 112, pp. 561-566 . https://doi.org/10.1053/gast.1997.v112.pm9024310
Gastroenterology, 112(2), 561-566. W.B. Saunders Ltd
ISSN: 0016-5085
DOI: 10.1053/gast.1997.v112.pm9024310
Popis: ‡The origin and neoplastic potential of gastric epithelial that is comparable with the adenoma-carcinoma sequence polyps remains an area of great interest, and treatment in the colorectum. 7 In the intestinal type of stomach choices are a topic of controversy. This report de- cancer, an accumulation of genetic mutations leading to scribes a patient diagnosed with three concurrent hy- oncogene activation and loss of tumor suppressor gene perplastic gastric polyps that were studied for genetic function may be associated with a gastric dysplasia-carcialterations. The polyps were investigated for alter- noma sequence. However, the specific genetic changes ations in the K-ras oncogene and the p53 tumor sup- accompanying this sequence are less well defined. 8 pressor gene and for p21 WAF1/Cip1 and MDM2 protein Activation of ras oncogenes, a frequent finding in colooverexpression. In addition, loss of heterozygosity at rectal neoplasms, is rare in the stomach, although it was several loci that are frequently involved in human can- reported in a subset of patients at high risk for stomach cer was analyzed, microsatellite instability, a hallmark cancer. 9,10 Activation of the K-ras oncogene by codon 12 of the ‘‘mutator’’ phenotype, was determined, and Eppoint mutations is a common and relatively early event stein‐Barr virus infection was investigated. All separate areas from the three independent polyps harbored in colorectal neoplasms. Alterations in the p53 tumor the same activating point mutation in codon 12 of the suppressor gene, frequently associated with the transition K-ras oncogene, indicating a clonal origin. DNA se- of an in situ lesion into an invasive neoplasm in the quence alterations in p53 were not found, although colorectum, 11 most likely play a similar role in the stomhigh p53 protein levels could be shown by immunohis- ach. 10,12 Mechanisms to disrupt p53 protein function intochemistry in areas of carcinoma within the largest clude missense mutations in exons 5 through 8, often polyp. No alterations in any of the other molecular accompanied by allelic loss of the remaining functional markers were observed. The results strongly favor a p53 allele. 13 The normal (wild-type) p53 protein, but clonal origin of the three independent gastric polyps not the altered p53 protein, binds specifically to DNA and support the notion that these hyperplastic polyps and acts as a transcription factor for several genes. 14 One may carry a risk for malignancy. of these genes, called WAF1 or Cip1, encodes a 21kilodalton protein (p21 WAF1/Cip1 ) that is a potent inhibitor for several cyclin-dependent kinases that control progres
Databáze: OpenAIRE
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