br Clinical implication of liver

Clinical implication of liver cancer stem cells in hepatocellular carcinoma HCC could be derived from either the putative periportal stem cells or from the transition duct cells or their progeny (hepatic genitor cells or oval cells). Recent reports have shown that CD133+ cells have stem cell characteristics in HCC as well as in other tumors. Therefore, we conducted a study to investigate HPC in HCC and their clinical significances. In our department, there were 42 patients (31 males, 11 females, aged 23–80 years old) with HCC, who accepted liver resection and yielded specimens which were sufficient for pathological studies from 2004 to 2007. Immunohistochemical studies were carried out with human monoclonal SCR 7 manufacturer against OV-6, CD133, CK-19, CD44 and AFP to investigate HPC in the tumors of HCC patients. The number of HPC cells was counted at 100× magnification under light microscopic examination. The following definitions were used: Grade 0, normal or <25; Grade 1, <25–50; Grade 2, 50–75; Grade 3, >75/field of 100× magnification. Clinical data and its relation with HPC were studied and biostatistical analysis was performed (Table 1). The difference was deemed significant if p value was <0.05. The results are as follows: (1) the architecture of the compartment between hepatocytes and bile ducts including the three cell types, the terminal bile duct cells, transition duct cells and the putative peri-portal liver stem cells, are shown in Figs. 1–3. These cells have been implicated as possibly giving rise to HCC; (2) HGC and hepatitis B and hepatitis C – HPC grading was higher in patients with HCC and hepatitis B or hepatitis C than in those with non-B or C hepatitis, as shown in Fig. 4. The higher incidence of HCC in hepatitis B infection is most probably related to the increased turnover of hepatocytes secondary to destruction of hepatocytes, leading to stimulation of proliferation of stem cells and other progeny early in the hepatocyte de-differentiation proliferation; (3) liver CSC could be identified and showed positive staining with CD133 or OV-6 within the liver cancer tissue, as shown in Fig. 5. The CD133+ cells were round in shape and smaller than malignant cells. The 1-, 3-, and 5-year survival rates for Grade 0 and Grades 1–3 were: 92%, 76%, and 69%, and 63%, 50%, and 50%, respectively (p = 0.073). The survival rates (Tables 2 and 3) were different due to the various gradings of CSC (Table 4), and the survival rate was better in the group of Grade 0 than that in Grades 1–3, with a non-significant difference as shown in Fig. 6.
Discussion Although the CSC model has existed for over 50 years, only recently have the techniques of modern stem cell biology begun to facilitate rapid progress in this field. It had been demonstrated formally that a single cell can generate a heterogenous cancer and self-renew by the isolated pure tumorigenic cancer stem cells. As pointed out earlier, and also in our present results, etiological factors, such as inflammation and viral hepatitis B and C, appear to contribute to the development of HCC by creating phenotypically altered hepatocytes or hepatic progenitor cells. A more recently proposed hepatic progenitor cell model for HCC tumorigenesis may provide a personalized approach for mentioning diagnosis and treatment strategies in these patients. HCC could be derived from progenitor cells or de-differentiated transformed cells, based on the observation that embryonic stem cells and CSC have similar biological behavior. Depending on the extent of genetic alteration, the tumor cells may remain benign or become malignant and even show metastatic potential. This could explain the heterogenicity in HCC morphology, clinical behavior and molecular profiles for tumorigenesis, as shown in Fig. 7. Therefore, the HCC tumor initiated by a multistep carcinogenesis event and by resulting in heterogenity in morphology with stem cells of positive specific phenotypes, appears to have the capability to be more aggressive.