Low Rate of Microsatellite Instability in Young Patients with Adenomas: Reassessing the Bethesda Guidelines

Velayos, Fernando S.; Allen, Brian A.; Conrad, Peggy G.; Gum, James; Kakar, Sanjay; Chung, Daniel C.; Truta, Brindusa; Sleisenger, Marvin H.; Kim, Young S.; Terdiman, Jonathan P.
May 2005
American Journal of Gastroenterology;May2005, Vol. 100 Issue 5, p1143
Academic Journal
BACKGROUND AND AIM: Screening adenomas for microsatellite instability (MSI) in patients younger than 40 yr of age has been recommended by the Bethesda Guidelines as a means of identifying patients at risk for hereditary nonpolyposis colorectal cancer (HNPCC). We sought to determine the rate of MSI in adenomas removed from individuals under 40 yr of age over a 5-yr period in a university general gastroenterology practice.METHODS: We identified patients between 18 and 39 yr of age with endoscopically removed adenomatous colorectal polyps. Patients with polyposis syndromes, inflammatory bowel disease, or colorectal carcinoma were excluded. A three-generation family history was obtained via telephone interview. Endoscopic and histology reports were reviewed. Adenomas were tested for MSI using theBAT26andBAT40microsatellite markers, and expression of the MSH2 and MLH1 proteins was assessed by immunostaining.RESULTS: A total of 34 patients had 46 adenomas removed endoscopically. Out of 34 patients, 14 (41%) had a family history of colorectal cancer and 3 were from Amsterdam criteria positive families. A total of 28 of 46 adenomas (61%) were distal to the splenic flexure. Polyps ranged in size from 2 to 20 mm and averaged 6.6 mm. Five polyps (11%) were tubulovillous adenomas, and the remainder were tubular adenomas. None of the polyps were serrated adenomas and none demonstrated high-grade dysplasia. Among the 40 adenomas available for testing, none demonstrated MSI using eitherBAT26(0/40) orBAT40(0/21), nor did any of the polyps tested demonstrate loss of either MSH2 or MLH1 expression (0/16).CONCLUSION: Screening adenomas from patients younger than 40 yr of age for MSI was ineffective in identifying potentially new cases of HNPCC. New strategies that improve on the current clinical and molecular screening methods should be developed so that at-risk individuals can be identified and referred for germline testing before developing their first cancer.(Am J Gastroenterol 2005;100:1143–1149)


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