To analyze the cell kinetics of
ulcerative colitis (UC)-associated dysplasia,
cyclin A,
cyclin D1,
cyclin E, cdk2, cdk4, p21(Waf1), and p27(Kip1) were immunohistochemically examined, in comparison with sporadic tubular
adenomas. Immunohistochemical labeling indices for each marker in
formalin-fixed
paraffin-embedded tissue sections were assessed in a total of 23 low-grade dysplasias, 27 high-grade dysplasias, and 14 invasive
adenocarcinomas associated with UC. For comparison, 21 sporadic tubular
adenomas with low-grade dysplasia, 33 with high-grade dysplasia, and 21 invasive
adenocarcinomas were also examined. In UC-associated dysplasias,
cyclin A and p27(Kip1) were located in the lower parts of the crypts and p21(Waf1) in the upper regions. In tubular
adenomas,
cyclin A, cdk4, p27(Kip1), and p21(Waf1) were all expressed in the upper parts of the crypts. The expression levels of
cyclin D1,
cyclin E, and cdk2 were low. The cell proliferation zone in UC-associated dysplasia is located towards the bases of the crypts with the strong expression of
cyclin A and p27(Kip1), in contrast to tubular
adenomas, which have their cell proliferation zone in the upper parts of neoplastic crypts. It is considered that
tumorigenesis with UC-associated dysplasia is of the bottom-up type, related to altered expression of
cyclin A and p27(Kip1).