The expression of vascular endothelial growth factor correlates with mutant p53 and poor prognosis in human breast cancer

Wild-type p53 protein has been shown to inhibit angiogenesis through thromb ospondin in the preclinical setting, Here, we determined the associations b etween the expression of the angiogenic factor vascular endothelial growth factor (VEGF) and the p53 status, including different mutation sites and ty pes, in primary breast cancer. Cytosols from 224 primary breast cancer pati ents were analyzed with an enzyme immunoassay for determination of human VE GF(165) protein content. p53 status was determined hv cDNA-based sequencing of the entire coding region, by immunohistochemistry (IHC). and by a p53 l uminometric immunoassay (I,IA) method. Statistically significant associatio ns was found between higher VEGF content and non-wild-type p53 status for a ll methods; sequence-based data (P = 0.0019), IHC data (P = 0.0068), and th e I,IA method (r = 0.427: P > 0.001), Highest VEGF values were detected in tumors with p53 insertions, deletions, and stop codon mutations (P = 0.0043 ). Combining p53 status and VEGF content resulted in additional prognostic information, relapse-free survival (RFS: P = 0.0377), overall survival (OS; P = 0.0319), and breast cancer corrected survival (BCCS: P = 0.0292). In m ultivariate analysis, the relative hazard increased when the VEGF data were added to the p53 status, with a relative hazard of 1.7 for RFS and 3.0 for BCCS, compared with 1.1 fur RFS and 1.4 for BCCS among the patients with e ither high VEGF content or p53 mutation. Higher VEGF content was statistica lly significantly correlated with a worse outcome fur patients with estroge n receptor-positive tumors receiving adjuvant tamoxifen: RFS (P = 0.0471), OS (P = 0.0134), BCCS (P = 0.0064), as well as in multivariate analysis wit h point estimates of 3.4 and 2.1 fur BCCS and RFS, respectively, VEGF expre ssion is related to p53 status in human breast cancer patients. Combining V EGF with p53 status resulted in better prognostic prediction.