title: Significance of vascular endothelial growth factor (VEGF)/soluble VEGF receptor-1 relationship in breast cancer.
abstract: Angiogenesis, the formation of new blood vessels, is controlled by a balance between positive and negative endothelial regulatory factors. Soluble vascular endothelial growth factor receptor-1 (sVEGFR1), a naturally occurring soluble form of VEGFR1, is a negative counterpart of the vascular endothelial growth factor (VEGF) signaling pathway, which has been characterized as one of the most important endothelial regulators in human tumor angiogenesis. In our study, we examined the expression of sVEGFR1 in 110 primary breast carcinomas, and assessed its clinical significance. Ninety-four of 110 tumors showed > or = 0.1 ng/mg protein of sVEGFR1 (range:0. 1-6.9 ng/mg protein; median: 1.03 ng/mg protein) as determined by a specific enzyme-linked immunosorbent assay (ELISA). Immunoblot analysis confirmed the presence of sVEGFR1 in breast tumor tissues. The levels of sVEGFR1 were correlated significantly with the levels of VEGF. There was no significant correlation between the levels of sVEGFR1 and any clinico-pathological factors including age, menopause, nodal involvement and hormone receptor status. A univariate prognosis analysis showed that the intratumoral VEGF status, as determined by ELISA, was a significant prognostic indicator, but sVEGFR1 status was not. In the combined analysis, however, the ratio of sVEGFR1 and VEGF levels provided more statistically significant prognostic value than VEGF status alone. Tumors in which the sVEGFR1 levels exceeded VEGF levels 10-fold had a markedly favorable prognosis. Multivariate analysis also demonstrated that the ratio of sVEGFR1 and VEGF was an independent prognostic indicator after nodal status. In conclusion, sVEGFR1, an intrinsic inhibitor of VEGF, frequently co-expressed with VEGF in primary breast cancer tissues. The intratumoral balance between sVEGFR1 and VEGF levels might be crucial for the progression of breast cancer.
authors.affiliation: Breast Unit, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Tokyo, Japan. maktoi77@wa2.so-net.ne.jp
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Bando
authors.forename: Taeko
authors.initials: T
authors.lastname: Ogawa
authors.forename: Mariko
authors.initials: M
authors.lastname: Muta
authors.forename: Carsten
authors.initials: C
authors.lastname: Hornig
authors.forename: Herbert A
authors.initials: HA
authors.lastname: Weich
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000098:blood supply* / Q000401:mortality / Q000628:therapy; D016228:Endothelial Growth Factors / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008222:Lymphokines / Q000032:analysis*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
chemical_list: D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1