Clinical significance of hepatic cancer stem cells

SummaryThe human liver consists of three types of liver cells: mature hepatocytes, cholangiocytes, and bipolar adult hepatic stem/progenitor cells (HPC). These three types of cell are commonly regarded as the primary targets of malignant transformation in the liver, if exposed to carcinogens in vivo or in vitro. Activation and proliferation of hepatic progenitor cells have been reported in precancerous conditions, such as chronic inflammation (hepatitis B/hepatitis C, alcoholic hepatitis and steatohepatitis). An origin of hepatocellular carcinoma (HCC) from hepatic progenitor cells is currently inferred from the fact that many tumors contain a mixture of mature cells and cells phenotypically similar to hepatic progenitor cells. In our series, there were 42 patients (31 males, 11 females, aged 23–80 years old) with HCC, who accepted liver resection, yielding specimens sufficient for pathological studies. Immunohistochemical studies were made with human monoclonal antibodies against OV-6, CD133, CK-19, CD44, AFP for investigating the HPC. HPC grading was higher in HCC patients with hepatitis B or hepatitis C and lower in those with non-B or non-C hepatitis. As regards the survival of HCC patients based on the grading of cancer stem cells (CSC) within the tumor, the group of Grade 0 showed a more favorable survival rate than that of Grade 1–3. The 1-, 3-, and 5-year survival rates of Grade 0 and Grade 1–3 were 92%, 76%, and 69%, and 63%, 50%, and 50%, respectively (p = 0.073). These liver CSC would be more resistant to chemotherapeutic agents than tumor cells with limited proliferative potential. In conclusion, we strongly believe that the contributions of HPC warrant research in patients with HCC. Without determining the characteristics of CSC, it is impossible to propose new treatment strategies.