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

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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.