Limits of diagnosis and molecular markers for early detection of ulcerative colitis-associated colorectal neoplasia

Abstract

The incidence of colorectal neoplasia has been increasing among patients with long-standing and extensive ulcerative colitis (UC), and therefore surveillance colonoscopy has been widely recommended. However, because UC-associated neoplasia is often difficult to detect endoscopically and to discriminate from inflammatory regenerative epithelium histologically, the efficacy of current surveillance remains unsatisfactory. In order to overcome these difficulties, adjunctive modalities for diagnosing UC-associated neoplasia, chromo- and magnifying endoscopy for endoscopic diagnosis and analysis of p53 alteration for histological diagnosis have been introduced. Furthermore, if it were possible to differentiate UC patients with long-standing and extensive colitis into subgroups with a high and a low risk of neoplasia, it would enable physicians to conduct more intensive surveillance with these modalities for patients at higher risk. Several molecular alterations of nonneoplastic epithelium in UC patients with neoplasia may be promising as markers for identifying individuals with UC at increased risk of neoplasia. We evaluated estrogen receptor (ER) methylation of nonneoplastic colorectal epithelium to clarify whether this epigenetic alteration can contribute to the prediction of increased neoplasia risk in UC patients and demonstrated that the ER methylation level in nonneoplastic epithelium was higher throughout the colorectum in patients with neoplasia than in those without. These results suggest that analysis of ER gene methylation may be potentially useful for identifying individuals at increased risk of neoplasia among patients with long-standing and extensive UC.