Mutations of p53 in Barrett's esophagus and Barrett's cancer: A prospective study of ninety-eight cases
Mutations of p53 in Barrett's esophagus and Barrett's cancer: A prospective study of ninety-eight cases
复制标题
DOI：
10.1016/s0022-5223(96)70441-5
复制
发表时间：
1996-02-01
影响因子：
6
通讯作者：
Roth, JA
中科院分区：
文献类型：
--
作者：
Schneider, PM;Casson, AG;Roth, JA
我们先前在Barrett食管中发现了p53突变，因此开始了一项多机构研究，以确定其作为恶性肿瘤标志物的意义。（37名男性和11名女性，平均年龄56.2岁）平均随访2.2年，患有巴雷特食管伴化生或发育不良，但没有恶性肿瘤的证据，Barrett食管被分类为化生，32例患者无异型增生证据，13例为低度异型增生，3例为高度异型增生，其他50例患者（46名男性和4名女性，平均年龄60.2岁）患有Barrett食管腺癌，来自正常胃或食管的组织，体液，和Barrett食管通过内窥镜活组织检查从Barrett食管或癌症患者或在对一些Barrett癌症患者进行手术期间获得用于脱氧核糖核酸分析，采用聚合酶链反应扩增p53基因第5~9外显子，进行单链构象多态性分析，对检测到的突变进行脱氧核糖核酸测序，来自单独患有Barrett食管并且没有异型增生或低度异型增生的患者的组织样本中没有一个具有任何p53突变，但是患有高度异型增生并且没有侵袭性恶性肿瘤证据的三名患者中的一名确实具有p53突变。然而，在患有Barrett癌症的50名患者中，23名（46%）在Barrett上皮、肿瘤、其中20例仅在肿瘤中（n = 16）或在肿瘤和Barrett's上皮中（n = 4）有p53突变，表明突变在癌变中起直接作用。在非恶性组中的1例和7例癌症患者中发现Barrett's上皮突变在三名癌症患者中，突变仅发生在巴雷特上皮中，表明这种突变也可能是基因组不稳定性的标志物。突变主要发现于外显子5，7，p53突变明显参与了一部分患者（46%）的Barrett癌发病机制，我们可以检测到癌前Barrett上皮突变的事实支持了p53突变可能是浸润性癌风险增加的患者的有用标志物的假设。
We had previously identified p53 mutations in Barrett's esophagus and therefore began a multiinstitutional study to determine their significance as a marker for malignancy, Ninety-eight patients from four institutions were studied, Forty-eight patients (37 men and 11 women, mean age 56.2 years) had Barrett's esophagus with metaplasia or dysplasia but no evidence of malignancy at a mean follow-up of 2.2 years, Barrett's esophagus was classified as metaplasia with no evidence of dysplasia in 32 patients, as low-grade dysplasia in 13, and as high-grade dysplasia in three, The other 50 patients (46 men and four women, mean age 60.2 years) had adenocarcinoma arising in Barrett's esophagus, Tissues from normal stomach or esophagus, humor, and Barrett's esophagus were obtained for deoxyribonucleic acid analysis by endoscopic biopsy from patients with Barrett's esophagus or cancer or during operations on some patients with Barrett's cancer, Exons 5 through 9 of the p53 gene were studied for mutations by single-strand conformational polymorphism analysis after polymerase chain reaction amplification, Mutations detected by single-strand conformational polymorphism analysis were confirmed by deoxyribonucleic acid sequencing, None of the tissue samples from patients with Barrett's esophagus alone and no dysplasia or low-grade dysplasia had any p53 mutations, but one of the three patients with high-grade dysplasia and no evidence of invasive malignancy did have a p53 mutation, Of the 50 patients with Barrett's cancer, however, 23 (46%) had p53 mutations in Barrett's epithelium, tumors, or both, Twenty of these patients had p53 mutations in the tumor only (n = 16) or in both tumor and Barrett's epithelium (n = 4), suggesting that the mutation plays a direct role in carcinogenesis, Mutations in Barrett's epithelium were found in one patient in the group without malignancy and in seven patients with cancer (one with no dysplasia, two with low-grade dysplasia, and five with high-grade dysplasia), In three patients with cancer, mutations occurred only in Barrett's epithelium, suggesting that such mutations may also be a marker for genomic instability, Mutations were predominantly found in exons 5, 7, and 8, and transitions from guanine to adenine were the most frequent changes, Mutations of p53 are clearly involved in the pathogenesis of Barrett's cancer for a subset of patients (46%), and the fact that we could detect mutations in premalignant Barrett's epithelium supports the hypothesis that p53 mutations may be a useful marker for patients at increased risk for development of invasive cancer.