文档介绍：Hepatocellular Carcinoma
Raphaël Saffroy
Paul Brousse Hospital – Villejuif
U602 Inserm/Paris 11 University - IFR 89
Pr Brigitte Debuire
December 2008
Hepatocellular Carcinoma
Introduction
1) Epidemiology
2) Principal characteristics of the disease
2) Molecular insights
The Biomarker Paradox
1) Complexity of the cancerous process
2) Different types of biomarkers
3) The biomarker paradox
Usual serum screening tests
1) Alpha-fetoprotein (AFP)
2) Other serum tumour markers
Molecular markers
1) The main ic alterations in the tumour
p53 /ß Catenin
MSI / LOH
2) Molecular markers outside the tumour : Circulating
tumour cells
3) Global genomic approaches
Conclusion
1
Introduction
Hepatocellular Carcinoma
115 / 100 000
> 15 / 100 000
5 / 100 000
the fifth most frequent malignant tumours worldwide
600 000 new cases every year
80% in developing countries
2-5 /
Incidence is rising : hepatitis C, cirrhotic patients
2
Etiology
Obesity Alcohol
Diabetes Viruses
Drugs Metabolic dis.
Ageing Aflatoxin B1
Steatosis CIRRHOSIS
Steato-hepatitis
Steatosis / Fibrosis
Microenvironment
Inflammation / Necrosis / Regeneration
Screening : on patients with cirrhosis, hepatitis
high risk subpopulations
Imaging, AFP
Treatments
Palliative : alcoholisation, cryotherapy, chemoembolization,
hormonotherapy
Curative : hepatectomy, transplantation
Prognosis
5 year survival < 20% ; France : 3000 deaths every year
recurrence following transplantation : 20 to 30%
Better selection of patients for transplantation
3
Exogenous and Endogenous Factors
Activation of promotor genes
Inactivation of suppressor genes
Genomic instability
Disturbance of growth and clonal expansion
Loss of differentiation
Invasion
Ectopic survival
Normal Hyperplasia Dysplasia Invasive Carcinoma
Epithelium Adenoma Carcinoma In situ and Metastasis
Inhibitors Local and systemic host elements Stimulator