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Association of downregulation of cyclin D1 and of overexpression of cyclin E with p53 mutation, high tumor grade and poor prognosis in hepatocellular carcinoma

Background/Aims: The major regulatory events leading to cell proliferation occur in the G 1 phase of cell cycle, and the deranged expression of G 1 cyclins is related to oncogenesis. In this study, we analyzed the aberrant expressions of cyclins D1 and E, and their role in hepatocellular carcinoma....

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Published in:Journal of hepatology 1998-08, Vol.29 (2), p.281-289
Main Authors: Peng, Shian-Yang, Chou, Sheng-Ping, Hsu, Hey-Chi
Format: Article
Language:English
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Summary:Background/Aims: The major regulatory events leading to cell proliferation occur in the G 1 phase of cell cycle, and the deranged expression of G 1 cyclins is related to oncogenesis. In this study, we analyzed the aberrant expressions of cyclins D1 and E, and their role in hepatocellular carcinoma. Methods: We examined paired hepatocellular carcinoma and liver RNAs taken from 71 patients who had been followed for more than 4 years after tumor resection, using reverse transcription-polymerase chain reaction supplemented with Northern blotting and immunohistochemistry. The genetic alterations of the p53 gene were also studied. Results: Downregulation of cyclin D1 mRNA was detected in 29 hepatocellular carcinomas (40.8%), while overexpression was detected in only 4 hepatocellular carcinomas (5.6%). Downregulation of cyclin D1 was associated significantly with large hepatocellular carcinomas ( p=0.0006) and poorly differentiated (grades III–IV) hepatocellular carcinoma ( p=0.057), but not seen in any of 15 minute hepatocellular carcinomas (≤2.5 cm in size). Cyclin E mRNA was overexpressed in 40 hepatocellular carcinomas, regardless of tumor size. Overexpression of cyclin E was significantly associated with poorly differentiated and invasive hepatocellular carcinoma ( p=0.001 and p=0.015, respectively). Downregulation of cyclin D1 and overexpression of cyclin E were significantly associated with the p53 mutation ( p=0.023 and p=0.005, respectively). Hepatocellular carcinomas expressing both down-regulation of cyclin D1 and overexpression of cyclin E had the worst 4-year survival ( p
ISSN:0168-8278
1600-0641
DOI:10.1016/S0168-8278(98)80014-7