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

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 > or = 90% or G2M > or = 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 dysplasial 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.

Effect of pregnancy on gastrointestinal transit.

In order to evaluate the possible effects of pregnancy-associated sex steroids on gastrointestinal function, we determined gastrointestinal transit times and sex steroid levels in 15 women during the third trimester of their pregnancies and again 4--6 weeks following delivery when gastrointestinal function had symptomatically returned to normal. Gastrointestinal transit time from ingestion of a liquid lactulose meal to its delivery to the cecum was determined by monitoring breath hydrogen concentrations at 10-min intervals. Gastrointestinal transit times were significantly prolonged in the third trimester of pregnancy, when progesterone and estradiol levels were increased, compared to the postpartum period. This study supports previous findings which suggest that increasing levels of progesterone and estradiol affect gastrointestinal function and therefore may contribute to gastrointestinal symptoms that often occur in pregnant women.

Gastrointestinal transit: the effect of the menstrual cycle.

Gastrointestinal transit time as well as serum estradiol and progesterone levels were measured in 15 normally menstruating women twice during their menstrual cycle, once in the follicular phase (days 8-10) when progesterone levels are low and once in the luteal phase (days 18-20) when progesterone levels are increased. Each subject had a progesterone rise during the luteal phase and onset of menses at the expected time documenting ovulatory cycles. Gastrointestinal transit time from ingestion of lactulose to the delivery of the disaccharide to the cecum was determined by monitoring breath hydrogen levels at 10-min intervals. Gastrointestinal transit time was significantly (p less than 0.01) prolonged in the luteal phase when progesterone levels were increased compared with the follicular phase. This study demonstrates that the menstrual cycle plays an important role in determining the gastrointestinal transit time in normally menstruating women.