Relationship between dysplasia, p53 protein accumulation, DNA ploidy, and Glut1 overexpression in Barrett metaplasia

Citation
M. Younes et al., Relationship between dysplasia, p53 protein accumulation, DNA ploidy, and Glut1 overexpression in Barrett metaplasia, SC J GASTR, 35(2), 2000, pp. 131-137
Citations number
53
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
ISSN journal
0036-5521 → ACNP
Volume
35
Issue
2
Year of publication
2000
Pages
131 - 137
Database
ISI
SICI code
0036-5521(200002)35:2<131:RBDPPA>2.0.ZU;2-1
Abstract
Background: There is a need for molecular markers of malignant progression in Barrett metaplasia (BM). The aim of this study is to determine the relat ionship between dysplasia, p53 protein accumulation, DNA ploidy, and Glut1 in BM. Methods: Sections of esophageal biopsy specimens from 120 patients w ith BM were evaluated for dysplasia, p53 protein, and Glut1 expression by i mmunohistochemistry, and DNA ploidy by Feulgen stain and image analysis. In cases with diploid DNA histograms, the percentage cells in the G0G1 and G2 M phases of the cell cycle were determined. Results: Of 108 diploid cases 1 9 (28%) of 69 cases with G0G1 greater than or equal to 90% or G2M greater t han or equal to 8.33% were p53-positive: in contrast to only 1 (3%) of 39 c ases with lower G0G1 or G2M (P = 0.0008). Of 32 p53-positive: cases 11 (32% ) were aneuploid, in contrast to none (0%) of 88 p53-negative cases (P < 0. 0001). Ten (91%) of Ii aneuploid cases were high-grade dysplasia/ adenocarc inoma (HGD/CA), compared with only 1 (1%) of 109 diploid casts (P < 0.0001) . Five (45%) Of 11 cases with HGD/CA were Glut1-positive, in; contrast to n one (0%) Of 109 cases without HGD/CA (P < 0.0001). Conclusions: Our data st rongly suggest that in BM, after oxidative DNA damage, as a result of gastr oesophageal reflux, there is an increase in the percentage of cells in the G0G1 or G2M phases of the cell cycle to enable repair of damaged DNA; in so me of these cases this is followed sequentially by p53 gene mutation and pr otein accumulation, DNA aneuploidy, HGD, and CA with or without Glut1 overe xpression. These events can be detected in routinely processed biopsy sampl es.