Abstracts
2002 Digestive Disease Week

# 107479 Abstract ID: 107479 Expression of Vascular Endothelial Growth Factor with its Receptor Flk-1 in Human Colon Carcinoma Liver Metastases
Jun Cheng, Richard E Slavin, Jennifer Gallagher, Guojing Zhu, Sean S Kohles, Emma J Patterson, Lee L Swanstrom, Paul D Hansen, Portland, OR

BACKGROUND: Vascular endothelial growth factor (VEGF) regulates tumor angiogenesis following binding to its receptor (Flk-1). The purpose of this study was to investigate VEGF/Flk-1 expression in human colon carcinoma liver metastases. METHODS: Immunohistochemical analyses using antibodies against VEGF, Flk-1, CEA, human endothelial cell (CD31), and Ki-67 antigen were performed on 35 archival paraffin-embedded specimens, which were collected from resected human colon cancer liver metastases. The intensity of staining for VEGF/Flk-1 and CEA was assessed on scale of 0 to 3+. Microvessel density (MVD) was quantitated by light microscopy (x200). A proliferation index (PI) was calculated as Ki-67 positive cells/total cells x 100%. RESULTS: There were 16 males and 19 females with a mean age of 61 years (range 39-76). All cases had strong CEA staining (2 to 3+). Both VEGF and Flk-1 exhibited predominantly cytoplasmic staining, and VEGF was also nuclear localized. VEGF expression was strong (2 to 3+) in 27 of 35 (77%), mild (1+) in 4/35 (11%), and four (11%) were negative. Flk-1 expression was strong in 24/35 (69%), mild in 10/35 (29%), and one (3%) was negative. The higher VEGF expression was related to a higher Flk-1 expression (p=0.0058 Fisher exact test). Meanwhile, normal human hepatocytes also expressed VEGF, but not Flk-1. VEGF/Flk-1 expression was not related to the tumor differentiation, CEA, MVD or PI (p>0.05). CONCLUSIONS: Colon cancer liver metastases did express VEGF and its receptor Flk-1. In addition, VEGF expression was associated with Flk-1 expression. The endocrine, paracrine and/or autocrine VEGF from cancer cells and even normal hepatocytes may bind to Flk-1 to stimulate metastatic cancer cell growth and tumor angiogenesis. VEGF may be useful as a marker to evaluate the surgical treatment in colorectal liver metastases. Flk-1 may be a potential target for antiangiogenic therapy in cancer.