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10.1245/s10434-007-9730-z
Annals of Surgical Oncology 15:962-971 (2008)
© 2008 Society of Surgical Oncology
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Original Article

Biology of Hepatocellular Carcinoma

Roberta W. C. Pang, PhD1, Jae Won Joh, MD2, Philip J. Johnson, MD3, Morito Monden, MD4, Timothy M. Pawlik, MD, MPH5 and Ronnie T. P. Poon, MS, PhD1

1 Centre for Cancer Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
2 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
3 Cancer Research UK Institute for Cancer Studies, The University of Birmingham, Birmingham, UK
4 Department of Surgery, Osaka University, Graduate School of Medicine, Osaka, Japan
5 Department of Surgery, John Hopkins School of Medicine, Baltimore, Maryland, USA

Correspondence: Address correspondence and reprint requests to: Ronnie T. P. Poon, MS, PhD; E-mail: poontp{at}hkucc.hku.hk

Hepatocellular carcinoma (HCC) is a common cancer in the world due to high prevalence of hepatitis B or C virus infection. Research in recent years has uncovered important molecular pathways involved in development and progression of HCC. Several genetic aberrations and molecular mechanisms responsible for initiation of hepatocarcinogenesis have been identified. Novel biomarkers for HCC are being developed for better detection and prognostication. Alpha-fetoprotein, the conventional marker of HCC, has limited sensitivity and specificity. Serum levels of isoforms of AFP based on differential lectin binding of the glycan moiety appear to be more sensitive and specific than total AFP level in early detection of HCC. The clinical usefulness of other HCC biomarkers such as des-{gamma}-carboxy prothrombin and glypican-3 are under investigation. HCC is an aggressive tumor with early vascular invasion and metastasis. Studies over the past two decades have elucidated the clinical predictors of outcome, leading to several staging systems for HCC based on clinical parameters. However, the predictive accuracy of clinical staging systems is limited. Recent studies suggested that biological factors may provide additional prognostic information. In particular, gene expression profiling appears to be a promising approach. Study of tumor angiogenesis in HCC reveals that the expression of angiogenic factors such as vascular endothelial growth factor and angiopoietins may also predict prognosis. The elucidation of tumor biology of HCC is of particular importance in the current era of rapid development of anti-cancer molecular targeting agents, which provide hope for an effective systemic therapy for HCC.

Key Words: Hepatocellular • Biomarkers • Biological factors • Angiogenesis • Molecular • Gene expression






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