Expression Of Survivin And VEGF In Malignant Fibrous Histiocytoma And Its Relationship With Angiogenesis

Background and Objective Survivin, a new member of the inhibitor of apoptosis family of proteins, regulates two essential cellular processes. It inhibits apoptosis and promotes cell proliferation and is the strongest inhibitor of apoptosis identified to date. Although upregulated in the majority of cancers, survivin is rarely expressed in normal healthy adult tissues. Angiogenesis is an essential step for tumor growth, playing a critical role in tumor invasion and metastasis. Tumors develop angiogenesis by secreting growth factors, stimulating endothelial migration and proliferation. Among these growth factors, VEGF is regarded as the main growth stimulatory factor in the tumor-related angiogenesis. In addition to inhibite apoptosis and promote cell proliferation, survivin involves in tumor angiogenesis. This study investigated the expression of survivin and vascular endothelial growth factor(VEGF) and microvessel density(MVD) assessed by monoclonal antibody CD34 in malignant fibrous histiocytoma (MFH), and explored their correlations with clinicopathologic features and angiogenesis of MFH.METHODS: 60 malignant fibrous histiocytoma specimens were collected from January 2005 to May 2010 at Bone and soft tissue surgery of Shandong Cancer Hospital. All specimens were pathologically reevaluated to confirm the initial diagnosis. The expression of survivin and VEGF was detected by immunohistochemistry assays in the tissue samples from 60 malignant fibrous histiocytoma and the data was quantitatively analyzed.The microvessel density (MVD) was determined by CD34 immunostaining of microvascular endothelial cells.RESULTS: 1.The positive rates of survivin and VEGF in malignant fibrous histiocytoma were 75.0% and 80.0%,respectively .Their common positive rate was 55.0%. 2.The expression levels of both survivin and VEGF in malignant fibrous histiocytoma were significantly related to tumor differentiation (P=0.015,P=0),clinical stage(P=0.01,P=0.033)and metastasis(P=0.038,P=0.024)respectively(P<0.05 for each group).Overexpression of both were related to poor prognosis: the survival rates were significantly higher in patients with negative expression than in those with positive expression. Survivin expression was positively correlated with VEGF expression (r=0.635,P<0.01).3.The MVD was significantly correlated with the size of the tumor (P=0.015), tumor differentiation (P=0.033),clinical stage(P=0.01)and metastasis(P=0.04), respectively(P<0.05 for each group).Expression of the survivin and VEGF was shown to be positively associated with MVD assessed by Spearmans correlation and factor analysis(r= 0.462,P<0.01;r=0.455,P<0.01).CONCLUSION: Survivin and VEGF were highly expressed in malignant fibrous histiocytoma, and positively correlated with differentiation, clinical stage, and prognosis.The detection of the combinated expression would be valuable in diagnostic and prognostic evaluation for malignant fibrous histiocytoma. Since survivin and VEGF regulated the angiogenesis of malignant fibrous histiocytoma, blocking the activity of survivin and VEGF may be a new way to inhibit angiogenesis.