Increased expression of cyclin D1 is an early event in multistage colorectal carcinogenesis

Background and Aims: Cyclin D1 gene amplification and/or overexpression occurs in several human cancers. The level of expression of cyclin D1 protein during the multistage process of human colon carcinogenesis was determined. Methods: Cyclin D1 protein abundance was determined by immunostaining samples of normal colonic mucosa (n = 23), transitional normal mucosa adjacent to adenomas or adenocarcinomas (n = 41), hyperplastic polyps (n = 8), adenomatous polyps (n = 35), and adenocarcinomas (n = 27), using a polyclonal anti-human cyclin D1 antibody. Results: Cyclin D1 nuclear staining occurred in 30% of adenocarcinomas and 34% of adenomatous polyps but not in hyperplastic polyps or normal or transitional mucosa. Nuclear staining did not correlate with sex, age, size, or dysplasia of the adenomatous polyps or with differentiation and Dukes' staging of the adenocarcinomas. Left-sided colon neoplasms showed nuclear staining more frequently than those right- sided lesions. Diffuse or supranuclear cytoplasmic staining occurred in about one third of hyperplastic polyps, adenomas, and adenocarcinomas and in transitional mucosa adjacent to adenocarcinoma. Conclusions: Increased nuclear expression of cyclin D1 occurs in around one third of colonic tumors as an early event during multistage process of colon carcinogenesis. Increased expression of cyclin D1 may perturb cell-cycle control in benign adenomas and thereby enhance tumor progression.