title: KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer detected by colonoscopy.
abstract: Colorectal cancer (CRC) is one of the most frequent cancers worldwide. Adenoma is the main precursor lesion and, recently, the serrated polyps were described as a group of colorectal lesions with malignant potential. The morphologic and biologic characterizations of serrated polyps remain limited. The aim of the present study was to determine the frequency of KRAS and BRAF mutations and microsatellite instability (MSI) in CRC precursor lesions, to evaluate the association between molecular, pathologic and morphologic alterations in precursor lesions and to compare with the alterations detected in CRC. A series of 342 precursor lesions were removed from 155 patients during colonoscopy. After morphologic classification, molecular analysis was performed in 103 precursor lesions, and their genetic profile compared with 47 sporadic CRCs. Adenomas were the main precursor lesions (70.2%). Among the serrated polyps, the main precursor lesion was hyperplastic polyps (HPs) (82.4%), followed by sessile serrated adenomas (12.7%) and traditional serrated adenomas (2.0%). KRAS mutations were detected in 13.6% of the precursor lesions, namely in adenomas and in HPs, but in no serrated adenoma. BRAF mutations were found in 9 (8.7%) precursor lesions, mainly associated with serrated polyps and absent in adenomas (P<0.001). High MSI (MSI-H) was absent in precursor lesions. In the 47 CCR cases, 46.8% exhibited KRAS mutation, 6.5% BRAF mutations and 10.6% MSI-H. This study confirms the role of KRAS and BRAF mutations in CRC carcinogenesis, a crucial step in implementing CRC screening strategies.
authors: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors: L S
authors: LS
authors: Yamane
authors: Department of Pathology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors: C
authors: C
authors: Scapulatempo-Neto
authors: Department of Endoscopy, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors: L
authors: L
authors: Alvarenga
authors: Department of Epidemiology and Biostatistics, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors: C Z
authors: CZ
authors: Oliveira
authors: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors: G N
authors: GN
authors: Berardinelli
authors: Department of Endoscopy, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors: E
authors: E
authors: Almodova
authors: Department of Endoscopy, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors: T R
authors: TR
authors: Cunha
authors: Department of Endoscopy, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors: G
authors: G
authors: Fava
authors: Department of Endoscopy, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors: W
authors: W
authors: Colaiacovo
authors: Department of Digestive Surgery, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors: A
authors: A
authors: Melani
authors: Department of Epidemiology and Biostatistics, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors: J H
authors: JH
authors: Fregnani
authors: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors: R M
authors: RM
authors: Reis
authors: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors: D P
authors: DP
authors: Guimarães
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D003111:Colonic Polyps / Q000235:genetics* / Q000473:pathology; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: 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