Serrated polyps of the large intestine: a molecular study comparing sessile serrated adenomas and hyperplastic polyps.
OBJECTIVE
To compare the molecular profile of a series of sessile serrated adenomas (SSAs) and hyperplastic polyps (HPs), in order to distinguish these lesions, SSAs having a potential role in the genesis of serrated adenocarcinomas through a serrated pathway in which methylation plays a key role.


RESULTS
Twelve HPs and sixteen SSAs of the right and left colon were investigated for microsatellite instability, DNA mismatch repair genes, p53, p16, and beta-catenin expression, MLH1 and p16 (CDKN2A) gene methylation, and KRAS and BRAF mutations. Both SSAs and HPs were microsatellite stable. MLH1 and MSH2 protein silencing, aberrant cytoplasmic expression and methylation of p16 were found to be exclusive to right-sided SSAs. The MLH1 promoter gene was frequently methylated in right-sided SSAs in contrast with HPs. Abnormal p53 and beta-catenin expression was present in both SSAs and HPs. BRAF and KRAS mutation were mutually exclusive, but KRAS mutation was present only in left-sided SSAs and HPs.


CONCLUSIONS
HPs and SSAs may be related lesions. However, at least right-sided SSAs differ from left-sided SSAs and HPs in the occurrence of MLH1 and p16 methylation, supporting the hypothesis that SSAs could be precursors of serrated adenocarcinomas.
Sandmeier
Dominique
D
Institute of Pathology, CHUV, Lausanne CH-1011, Switzerland.
Benhattar
Jean
J
Martin
Patricia
P
Bouzourene
Hanifa
H
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003111:Colonic Polyps / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053843:DNA Mismatch Repair; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D019942:Genes, p16; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007420:Intestine, Large / Q000378:metabolism / Q000473:pathology; D008745:Methylation; D018895:Microsatellite Repeats; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D004273:DNA, Neoplasm; C117307:KRAS protein, human; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051176:beta Catenin; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins