An insight into the genetic pathway of adenocarcinoma of the small intestine
An insight into the genetic pathway of adenocarcinoma of the small intestine
复制标题
DOI：
10.1136/gut.50.2.218
复制
发表时间：
2002-02-01
期刊：
影响因子：
24.5
通讯作者：
Bodmer, WF
中科院分区：
文献类型：
--
作者：
Wheeler, JMD;Warren, BF;Bodmer, WF
背景资料：虽然在大肠癌的腺瘤到癌的途径是很好的描述，在小肠的致癌机制仍然不清楚。Aims：本研究的目的是探讨候选基因的遗传途径的腺癌的小肠。主题和方法：共21个非家族性，非壶腹腺癌的小肠进行了分析。使用标准技术从福尔马林固定的石蜡包埋的组织中提取DNA。通过扩增BAT 26确定复制错误（RER）状态。应用聚合酶链反应-单链构象多态性和直接测序技术，对大肠腺瘤性息肉病（APC）基因突变簇区（MCR）进行了筛选。结果：14例男性，7例女性，平均年龄64岁（21-85岁），十二指肠腺癌10例，空肠腺癌7例，回肠腺癌4例。一个癌症（5%）被发现是RER+，所有肿瘤染色阳性的hMLH 1和hMSH 2。在APC基因的MCR中未检测到突变。β-连环蛋白在10个癌中（48%）表现出核表达增加，膜染色丧失。在8例癌症（38%）中发现E-钙粘蛋白膜表达缺失或减少。5例癌细胞核p53强阳性表达（24%）。结论：未检测到APC基因MCR突变，提示小肠腺癌与结直肠癌可能存在不同的遗传途径。E-cadherin和β-catenin的异常表达是常见的，反映了APC在该途径中的早期替代，其中在小肠腺癌中可能发现突变。
Background: Although the adenoma to carcinoma pathway in colorectal cancer is well described, the mechanisms of carcinogenesis in the small intestine remain unclear.Aims: The aim of this study was to investigate candidate genes in the genetic pathway of adenocarcinoma of the small intestine.Subjects and methods: A total of 21 non-familial, non-ampullary adenocarcinomas of the small intestine were analysed. DNA was extracted from formalin fixed paraffin wax embedded tissue using standard techniques. The replication error (RER) status was determined by amplification of BAT26. The mutation cluster region (MCR) of the adenomatous polyposis coli (APC) gene was screened using polymerase chain reaction single strand conformational polymorphism and direct sequencing. Immunohistochemistry was performed on formalin fixed paraffin wax embedded tissue using monoclonal antibodies for hMLH1, hMSH2, beta-catenin, E-cadherin, and p53.Results: Fourteen male and seven female patients with a median age of 64 years (range 21-85) presented with adenocarcinoma of the duodenum (10), jejunum (7), and ileum (4). One cancer (5%) was found to be RER+, and all tumours stained positive for hMLH1 and hMSH2. No mutations were detected in the MCR of the APC gene. beta-Catenin showed increased nuclear expression with loss of membranous staining in 10 cancers (48%). Absent or decreased membrane expression of E-cadherin was found in eight cancers (38%). Strong staining of p53 was found in the nucleus of five cancers (24%).Conclusion: We did not detect mutations in the MCR of the APC gene, and this suggests that adenocarcinoma of the small intestine may follow a different genetic pathway to colorectal cancer. Abnormal expression of E-cadherin and beta-catenin was common and reflects an early alternative to APC in this pathway in which mutations may be found in adenocarcinoma of the small intestine.