Chapter 5 Promoter CpG island hypermethylation patterns in polypoid and nonpolypoid colorectal adenomas

INTRODUCTION Colorectal adenomas, the precursor lesions of colorectal cancer (CRC), can have different phenotypes. One aspect of macroscopic variation is that of polypoid versus nonpolypoid adenomas. While the terms polyps and adenomas have long been used as synonyms, already in 1985 Muto et al coined the term " flat adenoma " for dysplastic lesions of the colorectal mucosa that are nonpolypoid. 1 For a long time, these flat or nonpolypoid adenomas were considered to rarely occur in Western countries, in contrast to Japan where they have been reported to represent 12-40% of colorectal adenomas and early carcinomas. 2,3 However, due to advances in endoscopic imaging techniques and increased awareness, a similar incidence of nonpolypoid lesions is now reported in Western countries. The issue of nonpolypoid versus polypoid adenomas is particularly relevant in the context of CRC screening. Colonoscopy with removal of precursor lesions has been demonstrated to reduce mortality from CRC in general. However, colonoscopy appear to have less effect on mortality in patients with proximal CRC. and interval cancer (cancers arising post-colonoscopy) are a major clinical problem. Nonpolypoid lesions can be easier missed by the endoscopist than polypoid lesions 6,14 and are predominantly located in the proximal colon. Therefore nonpolypoid adenomas may be an important cause of interval cancers in screening programs. Moreover, it has been suggested that nonpolypoid lesions have a higher progression risk due to a different tumor biology and could complete the adenoma to carcinoma sequence faster than polypoid adenomas. This suggested higher progression risk could be another reason why these lesions could cause interval cancers.