The Detection Of Apoptosis In Human Hepatocarcinogenesis

Objective: To study the expressions and correlations of apoptosis related components in the hepatocellular carcinogenesis and to identify the mechanism of hepatocarcinogenesis.Methods: cathepsin D, FADD and Ki-67 were detected by immunohistochemical staining in samples of chronic hepatitis, liver cirrhosis, paratumor cirrhosis, hepatocelluar carcinoma(HCC), and normal liver tissues. Apoptosis was detected by TdT-mediated x-dUTP nick end labeling (TUNED in these tissues.Results: No expressions of cathepsin D in normal liver tissues, but the expressions of the protein from chronic hepatisis, liver cirrhosis, paratumor cirrhosis to hepatocellular carcinoma(HCC) were gradually increased and the expressions of the protein was the highest in HCC. There were cytoplasmic staining patterns of positive cell of cathepsin D in the process of hepatocarcinogenesis. There was lower expressions of FADD in normal liver tissues, and its expressions was increased in chronic hepatitis and decreased in liver cirrhosis, paratumor cirrhosis and HCC yet, whereas there was no significant difference between the expressions in paratumor cirrhosis and in HCC(P > 0.05). There were nuclear staining pattern of FADD positive cell in chronic hepatitis, while cytoplasmic staining pattern in HCC. Except for chronic hepatisis, PI was gradually increased from liver cirrhosis, paratumor cirrhosis to HCC and was highest in HCC. No cellular proliferation was seen in normal liver tissues. Except for chronic hepatisis, AI was gradually increased from liver cirrhosis, paratumor cirrhosis to HCC and was lowest in normal liver tissues, its positive rate was highest in HCC. AI of Chronic hepatitis and liver cirrhosis were higher than their PI, PI of paratumor cirrhosis was little higher than its AI. Nevertheless, PI of HCC was higher than its AI obviously. AI was decreasing , while PI and cathepsin D were increasing with the depressions of HCC's differentiation level. There was statistical significance differentiation between well differentiation group and poor differentiation group (P < 0.05) .In all group tissues, AI was positive correlated with PI, Cathepsin D level was positive correlated with AI or PI(P < 0.05).There were significantly positive correlations between paratumor cirrhosis and HCC about Cathepsin D, FADD, AI and PI (P < 0.05) .Conclusions: These results indicated that the expressive abnormality of Cathepsin D and FADD should be involved in the occurrence and development of HCC.The level of AI, PI and Cathepsin D were associated with the differentiation degree of HCC. The intimate relationship between paratumor cirrhosis and HCC should support our presumed viewpoint that the paratumor cirrhosis may be a sequential lesion of precancerous cirrhosis around HCC. Cathepsin D could be used as one of a index to assess the malignancy degree of HCC. The reduce or loss of FADD may be a early-stage event in hepatocarcinogenesis. The infection of HBV could promote the nuclear staining pattern of FADD. Organism have protective reactions of oneself that reflected by the gradually increased AI. But the level of PI was obviously higher than AI, the loss of equilibrium between AI and PI was intimately associated with the occurrence and development of HCC.