Background/Aims. Cyclin D1 gene amplification and cyclin D1 protein overexp
ression have been reported in various human tumors, including hepatocellula
r carcinoma (HCC). However, their significance is still controversial. In t
he present study, we examined the expression of cyclin D1 and its relations
hips to p53 and Ki-67 in HCCs. Methods. The expression and topological dist
ribution of cyclin DI, p53 and Ki-67 in 50 cases of HCC were examined immun
ohistochemically, and the relationship between the expression of these prot
eins and their pathologic features was investigated. Results: Overexpressio
n of cyclin D1 was noted in 58% of the HCC cases, and significantly associa
ted with a well-differentiated histology and a low Ki-67 labeling index (LI
). Cyclin DI overexpression was also observed in all (7 of 7) dysplastic no
dules and in non-neoplastic hepatocytes. On the other hand, aberrant p53 ex
pression was detected in 36% of the cases, which showed positive relationsh
ips with poor differentiation, portal vein invasion, and KI-67 LI. Only eig
ht of the 50 cases examined (16%) were positive for both cyclin D1 and p53,
which showed only a small number of cyclin D1-positive cells. There was no
significant relationship between the expressions of cyclin D1 and p53. Con
clusions: Our results suggest that cyclin D1 overexpression may be an early
event in hepatocarcinogenesis and that it plays a role in tumor differenti
ation. In addition, cyclin DT expression is not correlated with tumor cell
proliferation in HCCs.