Cyclin D1 expression in the intestinal mucosa and tumors of Apc1638N mice.

Altered expression of cyclin D1 contributes to the development of several types of cancer, including colorectal cancer. This study examined cyclin D1 expression in 32 intestinal tumors in different stages of tumorigenesis in Apc1638N mice, a mouse model for human familial adenomatous polyposis (FAP). Three morphological patterns of expression of cyclin D1 in intestinal epithelial cells were found: nuclear, punctate-cytoplasmic and fine granular cytoplasmic. The nuclear pattern of cyclin D1 was detected in all of the tumors, including adenomas (n = 18) and adenocarcinomas (n = 14); this pattern was found predominantly in the tubular region of the tumors and in flat mucosa adjacent to a subset of the tumors (67% of adenomas and 57% of carcinomas). The punctate-cytoplasmic pattern of cyclin D1 expression was found in all adenocarcinomas and a majority of adenomas (80%), mainly in invasive and villous areas of the tumors; it was not found in normal flat adjacent mucosa suggesting that this pattern and altered cytoplasmic/nuclear expression were associated with tumor progression. Fine cytoplasmic granules were located in normal duodenum in the basal portion of the crypts and in colon in epithelial cells at the surface of the colonic crypts; in both duodenum and colon the number of cells with fine cytoplasmic granules significantly increased after feeding a Western-style diet. These altered patterns of expression of cyclin D1 may provide useful biomarkers of abnormal cell development for studies of tumorigenesis and the effects of chemopreventive agents.