Klump B, Holzmann K, Kühn A, Borchard F, Sarbia M, Gregor M, Porschen R
Department of Internal Medicine I, Eberhard-Karls-University, Tübingen, Germany.
Eur J Gastroenterol Hepatol. 1997 Aug;9(8):789-94. doi: 10.1097/00042737-199708000-00010.
Patients with ulcerative colitis are at an increased risk for developing colorectal neoplasms. p53 mutations and the occurrence of DNA aneuploidies are common events in the development of sporadic colorectal neoplasias. This study tried to determine the frequency of these events during the development of colitis-associated colorectal neoplasms.
DESIGN/METHODS: Four colectomy specimens with a total of 124 biopsies were investigated. DNA content was measured by flow cytometry and p53 protein expression was detected by immunohistochemistry. These results were correlated with histological findings.
DNA aneuploidies were found in 58 (46.8%), and p53 protein expression in 30 samples (24.2%). The presence of DNA aneuploidy as well as of p53 protein expression correlated with the histological characteristics of neoplastic transformation. In areas without dysplasias or with indefinite dysplasias, 31.5% of the samples showed DNA aneuploidies and in about 9% of the samples p53 protein expression could be detected; 33.7% of samples without or with indefinite dysplasias showed p53 protein expression and/or DNA aneuploidies.
These results show that the occurrence of DNA aneuploidies and nuclear p53 protein expression is a common event in the development of colitis-associated colorectal neoplasias. p53 protein expression seems to be an early event in this process. DNA aneuploidies occur even earlier and more frequently in the absence of p53 protein expression. Therefore, other genetic alterations besides p53 gene mutations might be involved in colitis-associated tumour development.
溃疡性结肠炎患者发生结直肠肿瘤的风险增加。p53突变和DNA非整倍体的出现是散发性结直肠肿瘤发生过程中的常见事件。本研究试图确定这些事件在结肠炎相关结直肠肿瘤发生过程中的频率。
设计/方法:对4例共124份活检的结肠切除术标本进行研究。通过流式细胞术测量DNA含量,通过免疫组织化学检测p53蛋白表达。将这些结果与组织学发现进行关联。
58份样本(46.8%)发现DNA非整倍体,30份样本(24.2%)检测到p53蛋白表达。DNA非整倍体以及p53蛋白表达的存在与肿瘤转化的组织学特征相关。在无发育异常或不确定发育异常的区域,31.5%的样本显示DNA非整倍体,约9%的样本可检测到p53蛋白表达;33.7%无或有不确定发育异常的样本显示p53蛋白表达和/或DNA非整倍体。
这些结果表明,DNA非整倍体的出现和核p53蛋白表达是结肠炎相关结直肠肿瘤发生过程中的常见事件。p53蛋白表达似乎是这一过程中的早期事件。在没有p53蛋白表达的情况下,DNA非整倍体出现得更早且更频繁。因此,除了p53基因突变外,其他基因改变可能也参与了结肠炎相关肿瘤的发生。