Younes M, Lechago J, Chakraborty S, Ostrowski M, Bridges M, Meriano F, Solcher D, Barroso A, Whitman D, Schwartz J, Johnson C, Schmulen A C, Verm R, Balsaver A, Carlson N, Ertant A
Dept. of Pathology, Baylor College of Medicine and The Methodist Hospital, Houston, Texas 77030, USA.
Scand J Gastroenterol. 2000 Feb;35(2):131-7. doi: 10.1080/003655200750024281.
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.
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.
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).
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.
巴雷特化生（BM）中需要恶性进展的分子标志物。本研究的目的是确定发育异常、p53蛋白积累、DNA倍性和BM中Glut1之间的关系。
对120例BM患者的食管活检标本切片进行评估，通过免疫组织化学检测发育异常、p53蛋白和Glut1表达，通过福尔根染色和图像分析检测DNA倍性。在DNA直方图为二倍体的病例中，确定细胞周期G0G1期和G2M期的细胞百分比。
在108例二倍体病例中，69例G0G1≥90%或G2M≥8.33%的病例中有19例（28%）p53呈阳性，相比之下，G0G1或G2M较低的39例病例中只有1例（3%）p53呈阳性（P = 0.0008）。在32例p53阳性病例中，11例（32%）为非整倍体，相比之下，88例p53阴性病例中无一例（0%）为非整倍体（P < 0.0001）。11例非整倍体病例中有10例（91%）为高级别发育异常/腺癌（HGD/CA），相比之下，109例二倍体病例中只有1例（1%）为HGD/CA（P < 0.0001）。11例HGD/CA病例中有5例（45%）Glut1呈阳性，相比之下，109例无HGD/CA病例中无一例（0%）Glut1呈阳性（P < 0.0001）。
我们的数据强烈表明，在BM中，由于胃食管反流导致氧化性DNA损伤后，细胞周期G0G1期或G2M期的细胞百分比增加，以修复受损的DNA；在其中一些病例中，随后依次发生p53基因突变和蛋白积累、DNA非整倍体、HGD以及有或无Glut1过表达的CA。这些事件可以在常规处理的活检样本中检测到。
