Wild-type p53 protein has been shown to inhibit angiogenesis through thrombospondin in thepreclinical setting, Here, we determined the associations between the expression of the angiogenic factorvascular endothelial growth factor (VEGF) and the p53 status, including different mutation sites and types,in primary breast cancer. Cytosols from 224 primary breast cancer patients were analyzed with an enzyme immunoassay for determination of human VEGF(165) protein content. p53 status was determined hv cDNA-based sequencing of the entire coding region, by immunohistochemistry (IHC). and by a p53luminometric immunoassay (I,IA) method. Statistically significant associations was found between higher VEGF content and non-wild-type p53 status for all methods; sequence-based data (P = 0.0019), IHC data (P = 0.0068), and the I,IA method (r = 0.427: P > 0.001), Highest VEGF values were detected in tumorswith 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 multivariate 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 patientswith either high VEGF content or p53 mutation. Higher VEGF content was statistically significantly correlated with a worse outcome fur patients with estrogen receptor-positive tumors receiving adjuvant tamoxifen: RFS (P = 0.0471), OS (P = 0.0134), BCCS (P = 0.0064), as well as in multivariate analysis withpoint estimates of 3.4 and 2.1 fur BCCS and RFS, respectively, VEGF expression is related to p53 statusin human breast cancer patients. Combining VEGF with p53 status resulted in better prognostic prediction.
2001. Vol. 61, no 5, 2256-2260 p.