ErbB2 overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human breast carcinoma

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Abstract
BACKGROUND The angiogenic factor vascular endothelial growth factor (VEGF)‐A plays an important role in breast cancer progression. However, the involvement of VEGF‐C and VEGF‐D, two newer members of the VEGF family, in breast carcinoma and their relationship with clinicopathologic parameters have not been clearly demonstrated. METHODS In this study, the expression levels of VEGF‐A, VEGF‐C, and VEGF‐D protein in 107 breast carcinoma cases and 22 nonmalignant breast tissue samples were examined by immunohistochemistry and quantitated by image analysis. RESULTS Higher expression of VEGF‐C and VEGF‐D was found in breast carcinomas than in nonmalignant breast tissue samples. Moreover, expression of VEGF‐A, VEGF‐C, and VEGF‐D was significantly and positively correlated with ErbB2 expression. High levels of VEGF‐A expression were associated with shorter disease‐free survival (DFS). Patients with tumors expressing high levels of VEGF‐C or VEGF‐D showed a notable trend for worse DFS, however, it was not statistically significant. The combination of VEGF‐A and VEGF‐C status predicted survival better than either marker alone. CONCLUSIONS Our study suggests that expression of the angiogenic and lymphangiogenic factors (i.e., VEGFs) might be regulated at least in part by ErbB2. In addition, the combination of VEGF‐A and VEGF‐C status may better predict prognosis of patients with breast carcinoma than VEGF‐A alone. Cancer 2002;94:2855–61. © 2002 American Cancer Society. DOI 10.1002/cncr.10553