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| Familial Adenomatous Polyposis of Colon |
| Etiology •Familial Adenomatous Polyposis (FAP) is also known as Adenomatous Polyposis Coli (APC) •FAP is caused by a mutation on chromosome 5q21 with a putative tumor suppressor gene named APC or DP2.5 •The mutation is inherited as a autosomal dominant •Mutations at the APC locus are acquired and not inherited in 20% of cases •The exact mutation at the APC locus is unique for each kindred, but variable between kindreds •If the mutation occurs in the proximal 4 exons of the APC gene, a limited form both pathologically and clinically is found called Attenutated APC (AAPC) •The greatest number of polyps are found with mutations in the midpoint of exon 15 |
| Pathogenesis •In the presence of the APC gene polyposis is inevitable but as the mucosa of the child shows no evidence of polyposis for a number of years it is not known if other factors, possibly environmental, may be required for phenotypic expression •There is evidence of abnormal proliferative activity in the normal appearing mucosa of APC patients as well as in areas of adenomatous proliferation •A number of other abnormalities involving mucin formation, cell adherence and chromosome instability have also been demonstrated, |
| Epidemiology •Inherited as an autosomal dominant in 80% 0f cases •APC will be found in <5% of patients with adenocarcinoma of the colon •No sex predominance |
| General Gross Description •The gross appearance in APC is usually diagnostic •The mucosa is studded with polyps of varying size •The predominant site may be colon or rectum depending on the specific kindred •A minimum of 100 polyps is required for the diagnosis, but up to several thousand have been described and the mean is 500 polyps at the time of diagnosis •Most lesions are small,under 5 mm, sessile with a smooth surface similar to hyperplastic polyps •As polyps get larger the surface develops the lobulated raspberry like surface of sporadic polyps and stalks develop •Early carcinoma may be present, but is usual not identifiable grossly •If frank carcinoma has developed it has the same appearance as carcinoma in sporadic cases |
| General Microscopic Description •The colorectal mucosa initially show adenomatous proliferation which is multifocal and involves individual crypts or small groups of crypts •Most polyps are small and without stalks •Tubular type polyps predominate, but as larger polyps develop, tubulovillous polyps may be seen •Increasing severity of dysplasia and development of carcinoma are identical to that described in the adenoma-carcinoma sequence in adenocarcinoma of the colon nd adenomas of the colon |
| Clinical Correlation •The onset of polyp formation in patients with APC is usually after age 15 •Colorectal carcinoma is seen beginning 10-15yrs. after the onset of visible polyps •It is believed that carcinoma will eventually occur in all patients with APC •In an APC kindred the risk of carrying the gene drops to 4% if no polyps have developed by age 30 •Screening members of an APC kindred has traditionally been done with colonoscopy usually starting in the second decade. However endoscopic screening is being replaced by molecular screening for evidence of the APC mutation •The treatment for APC is total colectomy or proctocolectomy, the age determined by the individuals physical and psychosexual development •APC may be associated with a number of other phenotypically distinct syndromes: Gardner's; Turcot's and MEA most commonly |
| References Gastrointestinal Polyposis Syndromes, Boland and Kim in Gastrointestinal Disease, Sleisenger MH and Fordtran JS ed, Philadelphia, WB Saunders, 1993 pp 1430-1436 |
| Familial Adenomatous Polyposis of Colon |
| Synopsis by: Martin Nadel, M.D. (T67000M82210)[360] |
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