TY - JOUR
T1 - Relationship between dysplasia, p53 protein accumulation, DNA ploidy, and Glut1 overexpression in Barrett metaplasia
AU - Younes, M.
AU - Lechago, J.
AU - Chakraborty, S.
AU - Ostrowski, M.
AU - Bridges, M.
AU - Meriano, Frank V.
AU - Solcher, D.
AU - Barroso, Alberto O.
AU - Whitman, D.
AU - Schwartz, J.
AU - Johnson, C.
AU - Schmulen, A. C.
AU - Verm, R.
AU - Balsaver, A.
AU - Carlson, N.
AU - Ertant, A.
PY - 2000
Y1 - 2000
N2 - Background: There is a need for molecular markers of malignant progression in Barrett metaplasia (BM). The aim of this study is to determine the relationship between dysplasia, p53 protein accumulation, DNA ploidy, and Glut1 in BM. Methods: Sections of esophageal biopsy specimens from 120 patients with BM were evaluated for dysplasia, p53 protein, and Glut1 expression by immunohistochemistry, and DNA ploidy by Feulgen stain and image analysis. In cases with diploid DNA histograms, the percentage cells in the G0G1 and G2M phases of the cell cycle were determined. Results: Of 108 diploid cases 19 (28%) of 69 cases with G0G1 ≥ 90% or G2M ≥ 8.33% were p53- positive, in contrast to only 1 (3%) of 39 cases 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 11 aneuploid cases were high-grade dysplasia/adenocarcinoma (HGD/CA), compared with only 1 (1%) of 109 diploid cases (P < 0.0001). Five (45%) of 11 cases with HGD/CA were Glut1-positive, in contrast to none (0%) of 109 cases without HGD/CA (P < 0.0001). Conclusions: Our data strongly suggest that in BM, after oxidative DNA damage, as a result of gastroesophageal 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 some of these cases this is followed sequentially by p53 gene mutation and protein accumulation, DNA aneuploidy, HGD, and CA with or without Glut1 overexpression. These events can be detected in routinely processed biopsy samples.
AB - Background: There is a need for molecular markers of malignant progression in Barrett metaplasia (BM). The aim of this study is to determine the relationship between dysplasia, p53 protein accumulation, DNA ploidy, and Glut1 in BM. Methods: Sections of esophageal biopsy specimens from 120 patients with BM were evaluated for dysplasia, p53 protein, and Glut1 expression by immunohistochemistry, and DNA ploidy by Feulgen stain and image analysis. In cases with diploid DNA histograms, the percentage cells in the G0G1 and G2M phases of the cell cycle were determined. Results: Of 108 diploid cases 19 (28%) of 69 cases with G0G1 ≥ 90% or G2M ≥ 8.33% were p53- positive, in contrast to only 1 (3%) of 39 cases 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 11 aneuploid cases were high-grade dysplasia/adenocarcinoma (HGD/CA), compared with only 1 (1%) of 109 diploid cases (P < 0.0001). Five (45%) of 11 cases with HGD/CA were Glut1-positive, in contrast to none (0%) of 109 cases without HGD/CA (P < 0.0001). Conclusions: Our data strongly suggest that in BM, after oxidative DNA damage, as a result of gastroesophageal 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 some of these cases this is followed sequentially by p53 gene mutation and protein accumulation, DNA aneuploidy, HGD, and CA with or without Glut1 overexpression. These events can be detected in routinely processed biopsy samples.
KW - Adenocarcinoma
KW - Barrett esophagus
KW - Cancer
KW - Dysplasia
KW - Esophagus
KW - Image analysis
KW - Immunohistochemistry
KW - Progression
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U2 - 10.1080/003655200750024281
DO - 10.1080/003655200750024281
M3 - Article
C2 - 10720109
AN - SCOPUS:0034001599
VL - 35
SP - 131
EP - 137
JO - Scandinavian Journal of Gastroenterology
JF - Scandinavian Journal of Gastroenterology
SN - 0036-5521
IS - 2
ER -