Expression of Ki 67 in hepatocellular carcinoma induced by diethylnitrosamine in mice and its correlation with histopathological alterations.

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and the prognosis still remains dismal, so the present work was planned to assess the prognostic value of Ki67 in mice model of HCC induced by diethylnitrosamine (DEN), in addition to its correlation to the histopathological changes. Forty male Swiss albino mice were randomly divided into two groups; group I 10 mice were served as controls and group II 30 mice were injected i.p with DEN at a dose of 75 mg/kg b.w once /week for three weeks then 100 mg/kg b.w for another 3 weeks. Mice were sacrificed after 6, 12 and 18 weeks from the beginning of the experiment. Liver specimens were processed for histopathological examination and immunohistochemical expression of Ki67. Results of histopathological study revealed spotty necrosis with enlarged nuclei and cholestasis 6 weeks after DEN injection. Proliferation of bile ducts, perivenous focal apoptosis and increased number of cells acquiring large nuclei were prominent after 12 weeks. Deleterious effect of DEN was obvious after 18 weeks; where HCC features were seen as sheets of malignant hepatocytes, multinodular areas of coagulative necrosis and nodule of ghosts' necrotic hepatocytes. Collagen deposition was time dependent and showed maximum level around and within nodules in HCC after 18 weeks. Immunohistochemical expression of Ki67 showed increased positivity after 6 and 12 weeks and the highest increase in the number of Ki67 positive cells after 18 weeks of DEN injection. Conclusion: Based on the previous data, it could be concluded that ki67 can be used as a biological marker for prognosis of HCC.