Blount P L, Ramel S, Raskind W H, Haggitt R C, Sanchez C A, Dean P J, Rabinovitch P S, Reid B J
Department of Medicine, University of Washington, Seattle 98195.
Cancer Res. 1991 Oct 15;51(20):5482-6.
Barrett's esophagus is a condition in which the stratified squamous epithelium of the esophagus is replaced by metaplastic columnar epithelium that predisposes to the development of esophageal adenocarcinoma. Allelic deletions of 17p and alterations of p53 including elevated p53 protein levels have been observed in many different tumors. To investigate the presence of 17p allelic deletions and p53 protein overexpression in Barrett's adenocarcinomas, we have combined the use of restriction fragment length polymorphism analysis, multiparameter flow cytometry, and DNA content cell sorting. The combined use of these methodologies permits the purification of aneuploid tumor cells for restriction fragment length polymorphism analysis of 17p allelic deletions and the evaluation of p53 protein expression by multiparameter flow cytometry in the same aneuploid tumor cell populations. We analyzed 15 aneuploid populations and one tetraploid populations from 13 Barrett's adenocarcinomas for 17p allelic deletions and p53 protein overexpression to determine whether both of these alterations are involved in carcinogenesis in Barrett's esophagus. Twelve of 13 tumors (92%) had 17p allelic deletions, and 8 of 13 tumors (62%) had p53 protein overexpression. Eight of the 12 tumors (67%) with 17p allelic deletions also had p53 protein overexpression. These data indicate that both 17p allelic deletions and p53 protein overexpression are frequently involved in carcinogenesis in Barrett's esophagus.
巴雷特食管是一种食管的复层鳞状上皮被化生的柱状上皮取代的病症,这种化生的柱状上皮易引发食管腺癌。在许多不同肿瘤中都观察到了17号染色体短臂(17p)的等位基因缺失以及包括p53蛋白水平升高在内的p53改变。为了研究巴雷特腺癌中17p等位基因缺失和p53蛋白过表达的情况,我们联合使用了限制性片段长度多态性分析、多参数流式细胞术和DNA含量细胞分选技术。这些方法的联合使用能够纯化非整倍体肿瘤细胞,用于分析17p等位基因缺失的限制性片段长度多态性,并在同一非整倍体肿瘤细胞群体中通过多参数流式细胞术评估p53蛋白表达。我们分析了来自13例巴雷特腺癌的15个非整倍体群体和1个四倍体群体,以确定这两种改变是否都参与了巴雷特食管的致癌过程。13例肿瘤中有12例(92%)存在17p等位基因缺失,13例肿瘤中有8例(62%)存在p53蛋白过表达。12例存在17p等位基因缺失的肿瘤中有8例(67%)也存在p53蛋白过表达。这些数据表明,17p等位基因缺失和p53蛋白过表达都频繁参与了巴雷特食管的致癌过程。