Low rate of microsatellite instability in young patients with adenomas: reassessing the Bethesda guidelines.
OBJECTIVE
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 the BAT26 and BAT40 microsatellite 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 either BAT26 (0/40) or BAT40 (0/21), nor did any of the polyps tested demonstrate loss of either MSH2 or MLH1 expression (0/16).


CONCLUSIONS
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.
Velayos
Fernando S
FS
Division of Gastroenterology and Colorectal Cancer Prevention Program, University of California, San Francisco, CA, USA.
Allen
Brian A
BA
Conrad
Peggy G
PG
Gum
James
J
Kakar
Sanjay
S
Chung
Daniel C
DC
Truta
Brindusa
B
Sleisenger
Marvin H
MH
Kim
Young S
YS
Terdiman
Jonathan P
JP
D048868:Adaptor Proteins, Signal Transducing; D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D018253:Adenoma, Villous / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000328:Adult; D020137:Base Pair Mismatch / Q000235:genetics; D002352:Carrier Proteins; D043171:Chromosomal Instability / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D003111:Colonic Polyps / Q000235:genetics / Q000473:pathology; D003113:Colonoscopy; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D007417:Intestinal Polyps / Q000235:genetics / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D011351:Proctoscopy; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein