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

为建立家族性腺瘤性息肉病(FAP)患者结肠切除术后监测指标，我们调查了十二指肠和小肠病变的临床病理特征和腺瘤性息肉病(APC)基因的胚系突变。在我们的25例FAP患者中，有10例十二指肠腺瘤凹陷。凹陷型腺瘤较隆起型腺瘤具有更高的异型增生级别和更高的增殖活性。观察十二指肠壶腹10年以上的18例中，有5例十二指肠壶腹发育不良。首次监测和末次监测的细胞增殖活性无差异。对19例FAP患者的回肠黏膜进行放大结肠镜观察。5例患者可见不同区域的微腺瘤。可以观察到。5名患者中有3名有直肠残端癌病史，而14名阴性回肠微腺瘤患者没有此类病史。这些发现表明，在FAP患者中，应仔细检查十二指肠凹陷性病变，回肠腺瘤可能是直肠癌的预测指标。应用聚合酶链式反应-单链构象多态性分析，在37例FAP患者中有15例检测到基因组DNA的APC突变。APC基因外显子15突变的患者有大量的大肠息肉和严重的结肠外表现。4例外显子4、5或9突变的患者初诊时结肠外表现较少，结直肠腺瘤较少，年龄超过40岁。后者的临床特征与最近描述的减弱型FAP一致。我们的观察表明，对APC的分析似乎为FAP的监测计划提供了线索。

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.