Expression Of Survivin, VEGF, Microvessel Density In Gallbladder Carcinoma Tissue And Their Clinical Correlations

ObjectivesGallbladder carcinoma is one of the common digestive malignant tumors, which has a poor prognosis. In recent years, gallbladder carcinoma incidence rate has showed a significant rise in China. The tumorigenesis and development of gallbladder carcinoma are complex processes concerned of many factors, the most important of which are tumor-induced angiogenesis and the unbalance of apoptosis and proliferation. Survivin,a novel member of inhibitor of apoptosis family of proteins,has recently been found in many common human cancers but not usually in normal tissues.Survivin,a molecule for the inter face between apoptosis and cell cycle,is expressed in the G₂/M phase of the cell cycle in a cycle-regulated manner. Association with microtubules of mitotic spindle regulates cell mitosis. Survivin binds the terminal effector proteases caspase-3 and- 7 to inhibit cell apoptosis.For mation of three-dimensional vascular tubes in vitro is associated with strong inductioninduction of survivin in endothelial cells. Vascular endothelial growth factor(VEGF), apro-angiogenic factor, can up-regulate survivin expression in endothelial cells.Strongly VEGF binding to its receptors through autocrine and paracrine pathway can stimulate cell proliferation resulting in the formation of new blood vassels and the tumor growth.There is a close correlation between the formation of microvessel and tumor growth and metastasis.The specificity of CD34 is higher than that of other vascular endothelial cell makers.The aim of this study is to evaluate the relationship between the expression of survivin, VEGF and the microvessel density(MVD) labeled by anti-CD34 monoclonal antibody and clinic pathologocal factors in gallbladder carcinoma, which will provide the oretical basis for the evaluation, therapy and prognosis of gallbladder carcinoma.Methods(1)Tissues pecimensused for this study were obtained from 42 gallbladder carcinoma, which were resected surgically or from 1997 to 2004 and all-confirmed pathologically. All the tissues were fixed in 10% neutral formalin and embedden in paraffin. (2) SP immunohistochemistry technique was used to detect the expression of survivin and VEGF and the number of microvessel density labelled by anti-CD34 monoclonal antibody in all tissues. (3) The data was analysized by statistical software SPSS10.0. One-way ANVOA, x² -test and t-test were used to analysize the difference between different groups. P value<0.05 was considered as statistically significantvalue.Results1 .The positive expression rates of surviving in gallbladder polypus were 0%,while 73.8% in gallbladder carcinoma. There existed significant difference of the positive rate of surviving between the groups each other(P<0.01). The positive expression rate of VEGF (69.1%) in gallbladder carcinoma was higher than that in gallbladder polypus (37.5%)(p<0.01).CD34 antigene was stained maily in the membrane of vascular endothelial cells. MVD of gallbladder carcinoma (26.71±4.53)was significantly higher than that of gallbladder polypus (22.86±3.94) (P <0.05).2. There was a higher positive expression rate of survivin in III+IV group(90.0%)than that in I + II group (59.1%) (P<0.05). The positive expression rate of survivin in high differentiation group (50.0%)were lower than that of middle/low differentiation group(83.3%) (P <0.05). There existed significant difference of the positive expression rate of survivin between the lymphnode metastasis positive group (84.9%) and the lymphnode metastasis negative group(33.3%),(P <0.01).No significant difference were exist in different type tissure of gallbladder carcinoma (P <0.05).3. There was a significantly higher positive expression rate of VEGF in III+IV group(85.0%)than that of in I + II group (54.6%) (P <0.05). There was a significantly difference of positive expression rate of VEGF between high differentiation group (58.3%) and middle/low differentiation group (73.3%)(P <0.05). There existed significant difference of the positive expression rate of VEGF between the lymphnode metastasis positive group (78.8%) and the lymphnode metastasis negative group(33.3%),(P <0.05).No significant difference were exist in different type tissure of gallbladder carcinoma. (P <0.05).4.There was a positive correlation of the positive expression between VEGF and survivin. MVD in cases with survivin-positive gallbladder carcinoma( 26.12±4.48) was higher that of negative case(23.35±4.20) (P <0.05). MVD in cases with EVGF-positive gallbladder carcinoma (26.60±4.93) was higher that of negative case(24.32±3.65)(P <0.05). MVD in cases both of surviving and EVGF-positive gallbladder carcinoma (27.86±4.12) was significant higher that of negative case (22.75±3.96) (P <0.05).Conclusions1 .The expression of surviving in gallbladder carcinoma shows a significant rise and a strong relationship with lymphrodem etastasis and clinical age, which suggests that the high expression of survivin may play an key role in gallbladder carcinogensis and development.2. The high expression of VEGF in gallbladder carcinoma shows a close correlation with lymphrodem etastasis and clinical age, which suggests that VEGF expression is closely related to gallbladder carcinogensis and development.3.Angiogenesis shows a strong relationship with growth, invasion,metastasis and development of gallbladder carcinogensis,which suggests MVD maybe a key index for reflecting the biological behavior and prognosis of gallbladder carcinogensis.4. There exists a positive correlation of the positive expression between VEGF and survivin, which suggests VEGF may be an important factor in inducing the up-regulation of survivin.5. There is a close correlation of survivin expression and angiogenesis in gallbladder carcinoma, which suggests survivin, an imporment factor in cell anti-apoptosis and angiogenesis, may become a new target for gene therapy of gallbladder carcinoma.