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BMC Cancer. 2012; 12: 298.
Published online Jul 19, 2012. doi:  10.1186/1471-2407-12-298
PMCID: PMC3474178
Tumor stromal vascular endothelial growth factor A is predictive of poor outcome in inflammatory breast cancer
Hugo Arias-Pulido,corresponding author1 Nabila Chaher,2 Yun Gong,3 Clifford Qualls,4 Jake Vargas,1 and Melanie Royce1
1Departments of Internal Medicine, The University of New Mexico Cancer Center, Albuquerque, NM, USA
2Department of Pathology, Centre Pierre et Marie Curie, 1, Avenue Battendier, Place May 1st, Algiers, Algeria
3Department of Pathology, The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
4Mathematics and Statistics, The University of New Mexico Cancer Center, Albuquerque, NM, USA
corresponding authorCorresponding author.
Hugo Arias-Pulido: harias/at/salud.unm.edu; Nabila Chaher: n.chaher/at/hotmail.com; Yun Gong: yungong/at/mdanderson.org; Clifford Qualls: cqualls/at/salud.unm.edu; Jake Vargas: javargas/at/salud.unm.edu; Melanie Royce: mroyce/at/salud.unm.edu
Received November 8, 2011; Accepted July 19, 2012.
Abstract
Background
Inflammatory breast cancer (IBC) is a highly angiogenic disease; thus, antiangiogenic therapy should result in a clinical response. However, clinical trials have demonstrated only modest responses, and the reasons for these outcomes remain unknown. Therefore, the purpose of this retrospective study was to determine the prognostic value of protein levels of vascular endothelial growth factor (VEGF-A), one of the main targets of antiangiogenic therapy, and its receptors (VEGF-R1 and -R2) in IBC tumor specimens.
Patients and Methods
Specimens from IBC and normal breast tissues were obtained from Algerian patients. Tumor epithelial and stromal staining of VEGF-A, VEGF-R1, and VEGF-R2 was evaluated by immunohistochemical analysis in tumors and normal breast tissues; this expression was correlated with clinicopathological variables and breast cancer-specific survival (BCSS) and disease-free survival (DFS) duration.
Results
From a set of 117 IBC samples, we evaluated 103 ductal IBC tissues and 25 normal specimens. Significantly lower epithelial VEGF-A immunostaining was found in IBC tumor cells than in normal breast tissues (P <0.01), cytoplasmic VEGF-R1 and nuclear VEGF-R2 levels were slightly higher, and cytoplasmic VEGF-R2 levels were significantly higher (P = 0.04). Sixty-two percent of IBC tumors had high stromal VEGF-A expression. In univariate analysis, stromal VEGF-A levels predicted BCSS and DFS in IBC patients with estrogen receptor-positive (P <0.01 for both), progesterone receptor-positive (P = 0.04 and P = 0.03), HER2+ (P = 0.04 and P = 0.03), and lymph node involvement (P <0.01 for both). Strikingly, in a multivariate analysis, tumor stromal VEGF-A was identified as an independent predictor of poor BCSS (hazard ratio [HR]: 5.0; 95% CI: 2.0-12.3; P <0.01) and DFS (HR: 4.2; 95% CI: 1.7-10.3; P <0.01).
Conclusions
To our knowledge, this is the first study to demonstrate that tumor stromal VEGF-A expression is a valuable prognostic indicator of BCSS and DFS at diagnosis and can therefore be used to stratify IBC patients into low-risk and high-risk groups for death and relapses. High levels of tumor stromal VEGF-A may be useful for identifying IBC patients who will benefit from anti-angiogenic treatment.
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