Imbalance between cell proliferation and cellular DNA fragmentation in hepatocellular carcinoma

Authors

  • Pui-Chee Wu,

    1. Departments of Pathology and Medicine, University of Hong Kong, Hong Kong, University of Florida, Gainesville, Florida, USA
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  • Victor Kar-Tai Lau,

    1. Departments of Pathology and Medicine, University of Hong Kong, Hong Kong, University of Florida, Gainesville, Florida, USA
    2. Section of Hepatobiliary Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Florida, Gainesville, Florida, USA
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  • Jane Wing-Sang Fang,

    1. Section of Hepatobiliary Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Florida, Gainesville, Florida, USA
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  • Vicky Ching-Ha Lai,

    1. Departments of Pathology and Medicine, University of Hong Kong, Hong Kong, University of Florida, Gainesville, Florida, USA
    2. Section of Hepatobiliary Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Florida, Gainesville, Florida, USA
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  • Ching-Lung Lai,

    1. Departments of Pathology and Medicine, University of Hong Kong, Hong Kong, University of Florida, Gainesville, Florida, USA
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  • Johnson Yiu-Nam Lau

    Corresponding author
    1. Section of Hepatobiliary Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Florida, Gainesville, Florida, USA
      Dr. Johnson YN Lau, Senior Director, Antiviral Therapy, Schering-Plough Research Institute, K-15-4-4650; 2015 Galloping Hill Road, Kenilworth, NJ 07033 USA
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Dr. Johnson YN Lau, Senior Director, Antiviral Therapy, Schering-Plough Research Institute, K-15-4-4650; 2015 Galloping Hill Road, Kenilworth, NJ 07033 USA

Abstract

Abstract: Aim/Background: Hepatocellular carcinoma (HCC) is known for its rapid growth. This study was undertaken to determine the expression of proliferative markers, apoptosis (DNA fragmentation) and oncogene products known to regulate apoptosis (p53, bcl-2) in HCC. Methods: 150 Chinese patients with HCC were studied (M:F 128:22, age 14–88 years), Immunohistochemistry was employed to detect cell proliferative markers (PCNA, Ki67), and oncogene products known to regulate apoptosis (p53, bcl-2). DNA fragmentation was determined by terminal dUTP nick end labeling (TUNEL). Results: 98% and 95% of HCC had PCNA (median 2+) and Ki67 (median 2+) detected respectively. TUNEL labeling was detected in only a small number of tumor cells (no labeling in 11%, median 1/1000 cell labeled, range: 0–70/1000 cells). There was no correlation between TUNEL labeling and the clinical parameters (sex, age, cirrhosis, and survival) and the expression of cell proliferative markers. p53 was detected in 53% of the patients (median 1+, range: 0–4+) and bcl-2 was detected in a small proportion of tumor cells in only 13% of the HCCs (range: 0–1+). The expression of p53 and Bcl-2 did not correlate with TUNEL labeling or the natural survival. Conclusions: Cell proliferation in HCC is unmatched by apoptosis, accounting for the rapid growth of this tumor. This lack of apoptosis in HCC is unrelated to the expression of p53 or bcl-2 over-expression.

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