Expression Of Thrombospondin-1 (TSP-1), Vascular Endothelial Growth Factor (VEGF) And P53 Protein In Breast Carcinoma: Correlation With Tumor Neovascularization And Metastasis

Purpose To determine the correlation of thrombospondm-l(TSP-l), vascular endothelial growth factor(VEGF) and p53 protein with neovasculanzation and metastasis in breast carcinoma. Methods 76 breast carcinomas and 20 benign breast lesions were studied on the expression of TSP-1, VEGF, p53 protein and FVIII-RAg with SP immunohistochemical technique, the extent of neovasculanzation was assessed quantitatively by computer-assisted image analysis system. Double-labelling immunohistochemical studies were performed to examine the expression and the histological distribution in situ of p53 and TSP-1, p53 and VEGF, TSP-1 and FVffl-RAg. Microvessel count (MVC) and the expressions of TSP-1, VEGF and p53 protein were evaluated in different invasive and metastatic status of breast carcinoma. Moreover, the expression of p53 protein in 16 cases was evaluated quantitatively by computer-assisted image analysis system; the results were contrasted with that of the semi-quantitative analysis.Result 60 cases for TSP-1 (78.9%), 61 cases for VEGF (80.3%) and 45 cases for p53 protein (53.9%) were positive respectively and the average MVC was 128.6 +43.7 in the breast carcinoma group. The expression of VEGF and p53 protein in carcinoma group was significant higher than benign group (P<0.05). Significant differences of the MVC and the expression of VEGF were observed among the benign lesions, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (P<0.05). It showed that MVC tended to increase with the malignant progression of tumors. VEGF level was found a significant association with MVC (P=0.007), but not related to lymph node status (P=0.39). TSP-1 immunoreactivity was identified in rumor stroma at a different degree of staining intensity, the level of its expression was not correlated with histologic type and lymph nodal status (PXX05), but inversely correlated with MVC (P=0.012). Furthermore a few blood vessles can be found in the region with strong TSP-1 staining while a marked vasculanzation was shown in the region with weak TSP-1 staining. TSP-1 deposition in stroma appeared to have a tendancy to increase with high VEGF expression in cancer cell. In addition, p53 protein level was found not related to invasion, metastasis and MVC (P>0.05), but shown significant association with the expression of VEGF and TSP-1 (PO.005). The expression of TSP-1, VEGF, p53 protein and MVC had no significant correlation with lymph nodal status in invasive ductal carcinoma (P>0.05), but MVC strongly correlated with VEGF expression. The tendancy of the results of semi-quantitative analysis showed a consistency with that of AOD, but different from that of VIODConclusions It is suggested that TSP-1 and VEGF play an important role in neovasculanzation and invasive growth in breast carcinoma Combining examination of the expression of VEGF and TSP-1 with MVC should be a better predictor for malignant degree and prognosis in breast carcinoma Before the breakthrough of theores and methods involved with stereological quantitative analysis, standard semi-quanntanve analysis in some degree is still an effective prognostic method.