The Expression And Correlation Of Survivin, BFGF And MVD In Pancreatic Carcinoma

Background and ObjectivePancreatic carcinoma is a common malignant tumor of the digestive system, which has an increasing incidence rate in recent years. Because pancreatic carcinoma is difficult to early diagnosis and prone to early invasion and metastasis, so the excision rate is very low. Therefore understanding the pathogenesy of pancreatic carcinoma, which is highly significant for diagnosis and treatment the pancreatic carcinoma. With the development of molecular biology, it is well known that apoptosis and angiogenesis play an important role in the process of generation and development of malignant tumour.Survivin, a new member of inhibitor of apoptosis protein family, has been found recently. Survivin is usually expressed in most malignancies, but can not detected in normal tissues. It is the most powerful inhibitor of apoptosis. Survivin binds the terminal effector proteases, caspase-3 and caspase-7 to inhibit cell apoptosis and promote cell proliferation. The expression of Survivin is cell-cycle dependent. It is expressed in the G₂/ M phase of the cell cycle and participates in the cycle-regulated manner of cytogenetic transcription. Formation of three-dimensional vascular tubes in vitro is associated with strong induction of Survivin in endothelial cells.Basic fibroblast growth factor ( bFGF ) is a stong pro-angiogenic factor. It can upregulate the Survivin expression in endothelial cells, stimulate cell proliferation, and promote the formation of new blood vassels and the tumor growth. Some studies manifested that bFGF can be expressed by tumor cells through autocrine or paracrine pathway, and promotes the oncogenesis and progression of carcinoma.Angiogenesis plays an important role in tumor growth, invasion and metastasis, and it is the foundation of the tumor survival. The microvessel density ( MVD ) is a reliable indication to evaluate angiogenesis of tumors. The specificity of CD34 is higher than that of other vascular endothelial cell makers which are used to label the MVD.In morden times, the pathogenesis of pancreatic carcinoma has not been known completely, and the correlation among Survivin, bFGF and MVD has not been reported yet. The expression of Survivin, bFGF and MVD labeled by anti-CD34 monoclonal antibody is detected by the Streptavidin-Peroxidse ( S-P ) immunohistochemistry technique in the pancreatic carcinoma tissue and normal pancreatic tissue. The aim is to analyze the correlation between the expression of Survivin, bFGF and MVD and the clinicalpathologic factors, to explore the interaction between apoptosis and angiogenesis in oncogenesis and progression of pancreatic carcinoma, and to provide a new adjuvant method for the diagnosis and therapy of pancreatic carcinoma.Materials and MethodsTissue specimens used for this study were obtained from 45 pancreatic carcinomas and 10 normal pancreas tissue samples. They were resected surgically in the first affiliated hospital of Zhengzhou university from January, 2000 to June, 2006, and all were confirmed pathologically. All the tissues were fixed in 10 % neutral formalin and embedden in paraffin. The expression of Survivin, bFGF and MVD was detected by the S-P immunohistochemistry technique in pancreatic carcinoma and normal pancreatic tissue, and the correlation of these results was analyzed. Statistical software SPSS 11.0. x² test, t-test and spearman rank correlation were used to analyze the difference between different groups. P value < 0.05 was considered as statistically significant value.Results1. The expression of Survivin in pancreatic carcinomaThe positive rate of Survivin expression was 77.78 % ( 35 / 45 ) in pancreatic carcinoma, while no expression of Survivin was detectable in normal pancreatic tissue (0 /10), and there was a significant difference between two groups ( P < 0.01). In the 45 cases of the pancreatic carcinoma tissue, the positive rates of Survivin expression were 41.7 % ( 5 /12 ) 84.2 % (16 /19) and 100.0 % ( 14 /14) in the high, moderate and poor differentiation group, respectively. And there was significant difference in the three groups ( P < 0.05 ). The positive rate of Survivin expression was 69.7 % ( 23 / 33 ) in clinical stage group I + II, and that was 100.0 % (12/12) in clinical stage group III+IV. There was a significant difference between two groups ( P < 0.05 ). The expression of Survivin had no correlated relationship with the sex, the age, the size of tumour, the location and the lymphnode metastasis in the pancreatic carcinoma tissue (P>0.05).2. The expression of bFGF in pancreatic carcinomaThe positive expression rate of bFGF was 66.67 % ( 30 / 45 ) in pancreatic carcinoma, and that was 20.00 % in normal pancreatic tissue ( 2 / 10 ). There was a significant difference between two groups ( P < 0.01 ). In the 45 cases of the pancreatic carcinoma tissue, the positive rate of bFGF expression was 57.6 % ( 19 / 33 ) in clinical stage group I + II, and that was 91.7 % ( 11 / 12 ) in clinical stage group III+IV. There was a significant difference between two groups ( P < 0.05 ). There was a significant difference of the positive expression rate of bFGF between the lymphnode metastasis positive group ( 80.8 %, 21 / 26 ) and the lymphnode metastasis negative group (47.4 %, 9 /19), ( P < 0.05 ). The expression of bFGF had no correlated relationship with the sex, the age, the size of tumour, the location and the tumor histological grade in the pancreatic carcinoma tissue (P > 0.05 ).3. The expression of MVD in pancreatic carcinomaThe MVD was 37.68±10.05 in the pancreatic carcinoma group, and that was 14.37±5.11 in the normal pancreatic tissue. There was a significant difference between two groups ( P < 0.01 ). In the 45 cases of the pancreatic carcinoma tissue, the MVD in clinical stage group III+IV ( 42.80±13.42) was much higher than that in clinical stage group I + II ( 28.56±7.09 ), and there was a significant difference between two groups ( P < 0.01 ). There was significant difference of MVD between the lymphnode metastasis positive group ( 44.79±15.03 ) and the lymphnode metastasis negative group ( 26.75±5.79 ), ( P < 0.01 ).The expression of MVD had no correlated relationship with the sex, the age, the size of tumor, the location and the tumor histological grade in the pancreatic carcinoma tissue (P > 0.05 ).4. The correlation of expression among Survivin, bFGF and MVD in pancreatic carcinomaIn the 45 cases of the pancreatic carcinoma tissue, there was a positive correlation of the positive expression between Survivin and bFGF ( r = 0.529, P < 0.01). The MVD was 40.40±9.27 in the positive expression group of Survivin, and that was 28.15±6.31 in the negative expression group. There was a significant difference in the two groups (t = 4.627, P < 0.01). The MVD was much higher in the positive expression group ( 42.58±7.52 ) of bFGF than that in the negative expression group ( 27.87±6.78 ). There was a significant difference between two groups (t = 6.349, P < 0.01).Conclusions1. The expression of Survivin, bFGF and MVD in pancreatic carcinoma shows a significant rise. It suggests that the high expression of them may play a crucial role in oncogenesis and progression of pancreatic carcinoma.2. There is positive correlation of the positive expression between Survivin and bFGF, and the expression of Survivin and bFGF has significant correlation with MVD in pancreatic carcinoma. The high expression of them indicates that they may contribute to tumor angiogenesis of pancreatic carcinoma.3. Survivin, bFGF and MVD may play a synergistic action in oncogenesis and progression of pancreatic carcinoma. Detecting the expression of Survivin, bFGF and MVD may conduce to study the regulated mechanism between apoptosis and angiogenesis and provide a new target for gene therapy of pancreatic carcinoma.