Expression Of Survivin, VEGF And CD34 In Colorectal Carcinoma Tissue And Their Clinical Significances

Background and objectives: Colorectal carcinoma is one of the common digestive malignant tumors, which has a poor prognosis. In recent years, colorectal carcinoma incidence rate has showed a significant rise in China, and the rate is moderately higher for urban residents. The tumorigenesis and development of colorectal carcinoma are complex processes concerned of many factors, the most important of which are tumor-induced angiogenesis and the unbalance of apoptosis and proliferation. Srvivin, 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 the interface 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 ceil mitosis. Survivin binds the terminal effector proteases caspase-3 and -7 to inhibit cell apoptosis. Formation of three-dimensional vascular tubes in vitro is associated with strong induction of survivin in endothelial cells. Vascular endothelial growth factor(VEGF), a stongly pro-angiogenic factor, can upregulate survivin expression in endothelial cells. 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, invasion 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 clinicopathologocal factors in colorectalcarcinoma, which will provide theoretical basis for the evaluation, therapy and prognosis of colorectal carcinoma.Materials and Methods: (1) Tissue specimens used for this study were obtained from 24 adenomas, 52 colorectal adenocarcinomas and 12 adjacent normal mucosa samples from the resection margins, which were resected surgically or endoscopically from 1997 to 1999 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 SPSS 10.0. 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 significant value.Results: 1. The positive expression rates of survivin in para-carcinomatous normal mucosa, adenoma and colorectal carcinoma were 0%, 33.33% and 65.38% respectively. There existed significant difference of the positive rate of survivin between the groups each other(P<0.05 for both). The positive expression rate of VEGF (69.23%) in colorectal carcinoma was higher than that in adenoma (37.50%) and in para-carcinomatous normal mucosa (8.33%), (P<0.01 for both).CD34 antigen was stained maily in the membrane of vascular endothelial cells. MVD of colorectal carcinoma (23.39 + 8.24) was significantly higher than that of adenoma (15.71 + 7.45) and that of normal mucosa (11.85 + 7.25), (P<0.01 for both).2. In colorectal carcinoma tissues, there was no difference of survivin expression between the group with the diameter of 5.0cm and over(75.00%) than the group with the diameter less than 5.0cm(57.14%), (P>0.05). No differene of survivin expression was found between the high differentiation group(60.00%) and middle/low differentiation group(70.37%),(P>0.05). There was no difference of the positive expression rate of survivin between the serosal or extraserosal infiltration group(69.23%) and subserosa group(61.54%),(P>0.05). There existed significant difference of the positive expression rate of survivin between the lymphnodemetastasis p...