The role of overexpression and gene amplification of cyclin D1 in intrahepatic cholangiocarcinoma

Background/Aims: Intrahepatic cholangiocarcinoma (ICC) is a primary liver m alignant tumor with an extremely poor prognosis, but less attention has bee n directed to factors related to molecular carcinogenesis, including cell c ycle proteins. We examined the expression and gene amplification of cyclin D1, the cell cycle regulating protein. Our objective was to evaluate correl ations with clinicopathological factors in ICC. Methods: Cyclin D1 overexpression and cellular proliferative activity (Ki-6 7 labeling index) were investigated immunohistochemically, and 20 cases wer e further investigated for cyclin D1 gene amplification, using differential PCR. We examined the correlation between the expression and gene amplifica tion of cyclin D1 and clinicopathological factors, including overall surviv al in patients with ICC. Results: Immunohistochemical analysis revealed an overexpression of cyclin D1 protein in 28 of 66 subjects with ICCs (42%). The cyclin D1 overexpressi on was associated with poor histological differentiation (P = 0.04), high c ellular proliferative activity (P < 0.01), and a poor prognosis (P = 0.02) by univariate analysis, although it is not an independent prognostic factor by multivariate analysis. Cyclin D1 gene amplification was confirmed in fi ve of the 20 patients. Of those five cases of ICC, all had poor histologica l differentiation, and four of the five ICCs (80%) showed evidence of cycli n D1 immunoreactivity. Conclusions: Overexpression and gene amplification of cyclin D1 are frequen t and contribute to dedifferentiation and cellular proliferative activity o f ICCs, and overexpression also indicates a poor prognosis for patients wit h ICC, (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.