High prevalence of sessile serrated adenomas with BRAF mutations: a prospective study of patients undergoing colonoscopy.
OBJECTIVE
Sporadic colorectal cancers with a high degree of microsatellite instability are a clinically distinct subgroup with a high incidence of BRAF mutation and are widely considered to develop from serrated polyps. Previous studies of serrated polyps have been highly selected and largely retrospective. This prospective study examined the prevalence of sessile serrated adenomas and determined the incidence of BRAF and K-ras mutations in different types of polyps.


METHODS
An unselected consecutive series of 190 patients underwent magnifying chromoendoscopy. Polyp location, size, and histologic classification were recorded. All polyps were screened for BRAF V600E and K-ras codon 12 and 13 mutations.


RESULTS
Polyps were detected in 72% of patients. Most (60%) were adenomas (tubular adenomas, tubulovillous adenomas), followed by hyperplastic polyps (29%), sessile serrated adenomas (SSAs; 9%), traditional serrated adenomas (0.7%), and mixed polyps (1.7%). Adenomas were more prevalent in the proximal colon (73%), as were SSAs (75%), which tended to be large (64% >5 mm). The presence of at least one SSA was associated with increased polyp burden (5.0 vs 2.5; P < .0001) and female sex (P < .05). BRAF mutation was rare in adenomas (1/248 [0.4%]) but common in SSAs (78%), traditional serrated adenomas (66%), mixed polyps (57%), and microvesicular hyperplastic polyps (70%). K-ras mutations were significantly associated with goblet cell hyperplastic polyps and tubulovillous adenomas (P < .001).


CONCLUSIONS
The prevalence of SSAs is approximately 9% in patients undergoing colonoscopy. They are associated with BRAF mutation, proximal location, female sex, and presence of multiple polyps. These findings emphasize the importance of identifying and removing these lesions for endoscopic prevention of colorectal cancer.
Spring
Kevin J
KJ
Conjoint Gastroenterology Laboratory, Queensland Institute of Medical Research, Herston, Brisbane, Australia.
Zhao
Zhen Zhen
ZZ
Karamatic
Rozemary
R
Walsh
Michael D
MD
Whitehall
Vicki L J
VL
Pike
Tanya
T
Simms
Lisa A
LA
Young
Joanne
J
James
Michael
M
Montgomery
Grant W
GW
Appleyard
Mark
M
Hewett
David
D
Togashi
Kazutomo
K
Jass
Jeremy R
JR
Leggett
Barbara A
BA
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D003111:Colonic Polyps / Q000235:genetics / Q000473:pathology; D003113:Colonoscopy; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D051153:Wnt Proteins / Q000502:physiology
D051153:Wnt Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf