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Studies on gene mutation and long-term clinical course in familial adenomatous polyposis

家族性腺瘤性息肉病基因突变及远期临床病程研究

基本信息

批准号：
10670520
负责人：
IIDA Mitsuo
金额：
$ 1.86万
依托单位：
KAWASAKI MEDICAL SCHOOL
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670520/
关键词：
familial adenomatous polyposis Hereditary colorectal cancer Apc gene mutation duodenal adenoma ileal adenoma depressed adenoma of the duodenum attenuated familial adenomatous polyposis surveillance 十二指腸乳頭部腺腫 PCR-SSCP法 APC遺伝子変異 Apc遺伝子

项目摘要

In order to establish the guideline for surveillance after colectomy in patients with familial adenomatous polyposis (FAP), we investigated clinicopathologic features in duodenal and small intestinal lesions and germline mutations in adenornatous polyposis coli (Apc) gene in patients with the disease. Among our 25 FAP patients, 10 patients had depressed adenomas in the duodenum. The depressed adenomas had higher grade of dysplasia and higher proliferative activity than the protruding adenomas. In 18 patients whose duodenal ampulla were surveyed for more than 10 years, the grade of dysplasia progressed in 5 patients. The proliferative activity was not different at the initial and the final surveillance. We then observed the ileal mucosa of 19 FAP patients by magnifying colonoscopy. In five patients, distinctive areas of microadenomas. Could be observed. Three of the five patients had prior history of cancer in the rectal remnant while 14 patients with negative ileal microadenoma did not have such history. These findings suggest that in FAP patients the duodenum should be surveyed carefully with regards to the depressed lesions, and that ileal adenoma may be predictive of rectal cancer during surveillance. Using PCR-SSCP, Apc mutation of genomic DNA could be identified in 15 of our 37 FAP patients. Patients with a mutation at exon 15 of Apc had profuse colorectal polyposis and severe extracolonic manifestations. Four patients with mutations at exon 4, 5 or 9 had less extra colonic manifestations, fewer colorectal adenomas and over 40 years of age at the initial diagnosis. The clinical features of the latter patients conformed to those recently described as attenuated FAP. Our observations suggest that the analysis of Apc seems to provide a clue for surveillance program in FAP.

为了建立家族性腺瘤性息肉病（FAP）患者结肠切除术后的监测指南，我们研究了FAP患者十二指肠和小肠病变的临床病理特征和粘附性结肠息肉病（Apc）基因的种系突变。在我们的25例FAP患者中，10例患者在十二指肠有凹陷的腺瘤。凹陷型腺瘤的异型增生程度和增殖活性均高于隆起型腺瘤。在18例十二指肠壶腹检查超过10年的患者中，5例患者的异型增生程度进展。增殖活性在初始和最终监测时无差异。对19例FAP患者的回肠粘膜进行放大结肠镜观察。在5名患者中，有明显的微腺瘤区域。是可以观察到的。5例患者中有3例有直肠残端癌既往史，而14例回肠微腺瘤阴性患者无此类病史。这些结果表明，在FAP患者的十二指肠应仔细调查有关凹陷的病变，回肠腺瘤可能是预测直肠癌在监测。应用PCR-SSCP技术检测37例FAP患者中15例存在Apc基因突变。Apc第15外显子突变的患者有大量的结直肠息肉病和严重的结肠外表现。4例外显子4、5或9突变患者的结肠外表现较少，结直肠腺瘤较少，初次诊断时年龄超过40岁。后者患者的临床特征符合最近描述的减毒FAP。我们的观察表明，APC的分析似乎为FAP的监测提供了线索。