title: Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer.
abstract: 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 (x200), 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.
authors.affiliation: Department of Cell Biology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Kitadai
authors.forename: C D
authors.initials: CD
authors.lastname: Bucana
authors.forename: K R
authors.initials: KR
authors.lastname: Cleary
authors.forename: L M
authors.initials: LM
authors.lastname: Ellis
mesh_terms: D000236:Adenoma / Q000098:blood supply; D043925:Angiogenesis Inducing Agents / Q000032:analysis*; D002455:Cell Division; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology; D016228:Endothelial Growth Factors / Q000032:analysis*; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D000091344:Filaggrin Proteins; D006801:Humans; D008222:Lymphokines / Q000032:analysis*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D017978:Receptors, Growth Factor / Q000032:analysis*; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D043925:Angiogenesis Inducing Agents; D016228:Endothelial Growth Factors; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D008222:Lymphokines; D018809:Proliferating Cell Nuclear Antigen; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor