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Expression of Vascular Endothelial Growth Factor and Its Receptor, KDR, Correlates with Vascularity, Metastasis, and Proliferation of Human Colon Cancer
Yutaka Takahashi, Yasuhiko Kitadai, Corazon D. Bucana, Karen R. Cleary and Lee M. Ellis
Yutaka Takahashi
Yasuhiko Kitadai
Corazon D. Bucana
Karen R. Cleary
Lee M. Ellis
DOI: Published September 1995
We studied the correlation between expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and their receptors with vascularity, metastasis, and proliferative index of human colon cancers. Immunohistochemical analyses using antibodies against VEGF, bFGF, their receptors (KDR, flt-1, bek, and flg), factor VIII, and proliferating cell nuclear antigen were carried out on archival specimens of 52 human colon carcinomas and 10 adenomas. Vessels were quantitated by light microscopy (×200), and the intensity of staining for VEGF and bFGF was assessed on a scale of 0–3+. The presence or absence of immunostaining for KDR, flt-1, bek, and flg was evaluated in endothelial cells, and proliferation was determined by counting the number of proliferating cell nuclear antigen-positive cells per 500 tumor cells. Expression of VEGF and KDR was higher in metastatic than in nonmetastatic neoplasms and directly correlated with the extent of neovascularization and the degree of proliferation, whereas expression of bFGF, flt-1, bek, and flg did not differ among tumor types. Vessel counts were greater in metastatic tumors than in nonmetastatic tumors. These findings support the hypothesis that VEGF is an important angiogenic factor in primary and metastatic human colon cancer. VEGF expression and vessel counts may aid in predicting patients at risk for metastasis from colon cancer.
↵1 This work was supported in part by American Cancer Society Cancer Development Award 94-21 (L. M. E.).
↵2 To whom requests for reprints should be addressed, at The University of Texas M. D. Anderson Cancer Center, Texas Medical Center, Box 106, 1515 Holcombe Boulevard, Houston, TX 77030.
Received June 5, 1995.
©1995 American Association for Cancer Research.
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Cancer Res September 15 1995 (55) (18) 3964-3968;
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