Involvement of the serrated neoplasia pathway in inflammatory bowel disease-related colorectal oncogenesis.
The purpose of this study is to identify colorectal serrated lesions in the inflammatory mucosa of inflammatory bowel disease (IBD), to characterize their molecular status based on BRAF and KRAS mutations, mismatch-repair (MMR) deficiency and microsatellite instability (MSI), and to verify that these molecular alterations are specific to the 'serrated neoplasia pathway' in IBD. Neoplastic lesions from 36 patients with IBD were reviewed retrospectively, including 13 adenocarcinomas (1 mucinous and 12 conventional), 28 dysplasias [1 traditional serrated adenoma (TSA) and 27 conventional adenomas] and 1 hyperplastic polyp (HP). Both the HP and TSA exhibited the V600E BRAF mutation without MSI or MMR deficiency. The mucinous adenocarcinoma, close to the TSA, exhibited the BRAF mutation and MSI with loss of hMLH1. No KRAS mutations were found in these 3 lesions, and no BRAF mutations were found in the conventional ones. Serrated lesions exist in the inflammatory mucosa of IBD and are associated with a characteristic molecular profile, i.e. the appearance of the BRAF mutation as early as the hyperplastic polyp stage followed by MSI at the carcinoma stage. We therefore identified the serrated neoplasia pathway in IBD-related colorectal oncogenesis.
Bossard
Céline
C
INSERM U539, Faculté de Médecine, 1 rue Gaston Veil, 44035 Nantes Cedex 1, France. u539@nantes.inserm.fr
Denis
Marc G
MG
Bézieau
Stéphane
S
Bach-Ngohou
Kalyane
K
Bourreille
Arnaud
A
Laboisse
Christian L
CL
Mosnier
Jean-François
JF
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000473:pathology; D003111:Colonic Polyps / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D053843:DNA Mismatch Repair; D004273:DNA, Neoplasm / Q000032:analysis; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000473:pathology; D053842:Microsatellite Instability; D009154:Mutation; D010641:Phenotype; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics*
D004273:DNA, Neoplasm; D005819:Genetic Markers; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins