Expression Of Survivin And CyclinD1 Genes In Primary Hepatocellular Carcinoma And Their Relationship

1. Backgroud and ObjectivesHepatocellular carcinoma (HCC) is a malignant tumor with high incidence and mortality all over the world especially in China. The main therapies for HCC including surgery, chemical therapy, radio therapy and immunotherapy et al. Though great development has been achieved in technology, the 5 year survival rate remains very low. However, a new therapy which depends on molecular targets is showing its prosperity in clinical study.Survivin is a new member of inhibitor of apoptosis proteins (IAP) family. Survivin is found to express mainly in developing embryonic tissues and most human malignant tumor tissues, but not in the adult differentiated tissues. Current studies show that survivin has double regulating effects on apoptosis and cell cycle. By acting directly on caspases, survivin mainly inhibit the activity of Caspase-3 and Caspase-7, or interfer the activity of Caspase-9, block the common channel of apoptosis causes by various stimulation. Survivin distinctively expresses in the G2/M phase of the cell cycle, by combining with microtubules of mitotic spindle, partcipate the transcription regulation of genes. Survivin's selective expression in tissues and its special activity on the inhibition of cell apoptosis suggest that it is likely to become a special marker both in diagnosis and a potential therapeutic target in HCC.CyclinD1 is an important cellular proliferation factor and oncogene which is confirmed in recent years. It can promote cell cycles by accelerating the G1-S stages. Many researches have proved that there is a relationship between CyclinDl gene amplification and (or) over-expression with the occurrence, development and prognosis of HCC.S-P immunohistochemical staining was employed to detect the expression of survivin and cyclinDl genes in 50 HCC tissues and 20 normal liver tissues, to investgate the significance of survivin and cyclinDl with the possible carcinogenesis mechanism and their relationship in HCC, to suggest a new idea on the gene therapy of HCC. 2. Materials and Methods2.1 Materials: 50 paraffin specimens of HCC cases from 2001 to 2003, which were pathologically proved to be hepatocellular carcinoma, were collected from the Department of Hepatobiliary Surgery of Jinan Military Region General Hospital. 20 specimens of normal liver tissues were employed as the control.2.2 Methods: All the specimens are fixed by formalin, embedded by paraffin, sliced serially, marked with immunohistochemical markers by rabbit anti-human Survivin polyclonal antibody, CyclinD1 polyclonal antibody, and colored by DAB color appearance system to show out their expression in those specimens. Data of groups are analyzed statistically, together with their clinical pathological data. To probe into the relation between expression of the two proteins in 50 HCC tissues and 20 normal liver tissues and the clinical pathological symptoms of HCC, followed by a survey in prognosis. 3. Results3.1 The positive rate of survivin expression in HCC were 66.0%(33/50), which was significantly higher than that in normol liver tissues (negative expression) (P<0.001), the expression of survivin was correlated with intrahepatic dissemination and multiple masses (P=0.019,P=0.030) .3.2 The positive rate of cyclinDl expression in HCC was 44.0%(22/50), which was significantly higher than that in normol liver tissues (negative expression) (P<0.001), the expression of cyclinD1 was correlated with intrahepatic dissemination and tumor grade (P=0.035,P=0.036)3.3 There was a positive correlation between survivin expression and cyclinD1 expression (r=0.466, P<0.001) . The high survivin and cyclinD1 expression was associated with the survival stage less than three years (P=0.018, P=0.013) .4. ConclusionsThe study suggests that survivin and cyclinD1 might play certain roles in the oncogenesis and progression of HCC, but to different extent. Survivin and cyclinD1 could be valuble factors on prognosis of HCC. Combining detection of survivin and cyclinD1 gene products could supply certain evidence on prognosis of primary hepatocellular carcinoma.