Prospective study of cyclin D1 overexpression in Barrett's esophagus: Association with increased risk of adenocarcinoma

Background: Esophageal adenocarcinoma commonly arises from a precancerous c ondition, Barrett's esophagus, in which the normal squamous epithelium is r eplaced by a columnar cell-lined epithelium. Genetic alterations occurring in this process could serve as biomarkers for the risk of malignant progres sion, improve surveillance, and contribute to early diagnosis. We examined two potential biomarkers, cyclin D1 and p53, in a prospective cohort of Bar rett's esophagus patients. Methods: A total of 307 patients were enrolled i n an endoscopic surveillance cohort, and esophageal biopsy specimens were c ollected at each endoscopy, Incident cases of adenocarcinoma were matched t o control patients within the cohort by duration of follow-up, age, sex, an d length of columnar cell-lined epithelium at recruitment. Biopsy specimens were analyzed for cyclin D1 and p53 protein levels by immunohistochemistry . Statistical tests were two-sided. Results: A total of 12 cases of adenoca rcinoma occurred within the follow-up period, and tumor biopsy specimens fr om 11 cases stained positive for cyclin D1, Biopsy specimens from eight of these patients taken at recruitment also stained positive for cyclin D1, A case-control analysis of biopsy specimens obtained at recruitment revealed a statistically significantly increased risk of progression to adenocarcino ma in Barrett's esophagus patients whose biopsy specimens were cyclin D1 po sitive (odds ratio [OR] = 6.85; 95% confidence interval [CI] = 1.57-29.91; P = .0106) but not in patients whose biopsy specimens were p53 positive (OR = 2.99; 95% CI = 0.57-15.76; P = .197), Conclusions: Cyclin D1-positive st aining could be a useful biomarker in identifying Barrett's esophagus patie nts at high risk of esophageal adenocarcinoma, Given the complexity of gene tic alterations in the natural history of this cancer, additional biomarker s will be required to increase the sensitivity and specificity of molecular diagnosis.