Heterogeneity of colorectal adenomas, the serrated adenoma, and implications for screening and surveillance.
Current algorithms for screening and surveillance for colon cancer are valuable, but may be limited by the underlying nature of the targeted neoplastic lesions. Although part of the success of adenoma removal relates to interruption of so-called "adenoma-carcinoma sequence", an alternate serrated pathway to colon cancer may pose difficulties with the ultimate results achieved by traditional colonoscopic methods. The endpoint carcinoma in this unique pathway may be derived from a dysplastic serrated adenoma. These tend to be located primarily in the right colon, especially in females, and are frequently associated with co-existent colon cancer. Unfortunately, however, there are few, if any, other identifiable risk factors, including age or family history of colon polyps or colon cancer. Moreover, this alternate serrated pathway may itself also be quite biologically heterogeneous as reflected in sessile serrated adenomas (SSA) with virtually exclusive molecular signatures defined by the presence of either BRAF or KRAS mutations. Screening algorithms in the future may need to be modified and individualized, depending on new information that likely will emerge on the natural history of these biologically heterogeneous lesions that differs from traditional adenomatous polyps.
Department of Medicine (Gastroenterology), University of British Columbia Hospital, 2211 Wesbrook Mall, Vancouver V6T 1W5, Canada. hugfree@shaw.ca
Hugh-James
HJ
Freeman
D000236:Adenoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000465:Algorithms; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D009154:Mutation / Q000235:genetics; 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
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