Tumor stromal vascular endothelial growth factor A is predictive of poor outcome in inflammatory breast cancer

BMC Cancer

Research Article

Nabila Chaher¹  Yun Gong²  Jake Vargas³  Melanie Royce³  Hugo Arias-Pulido³  Clifford Qualls⁴ 

[1] Department of Pathology, Centre Pierre et Marie Curie, 1, Avenue Battendier, Place May 1st, Algiers, Algeria;Department of Pathology, The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;Departments of Internal Medicine, The University of New Mexico Cancer Center, Albuquerque, NM, USA;Mathematics and Statistics, The University of New Mexico Cancer Center, Albuquerque, NM, USA;

关键词: Epidermal Growth Factor Receptor;    Tamoxifen;    Bevacizumab;    Inflammatory Breast Cancer;    Normal Breast Tissue;   

DOI  :  10.1186/1471-2407-12-298

 received in 2011-11-08, accepted in 2012-07-19,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundInflammatory 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 MethodsSpecimens 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.ResultsFrom 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).ConclusionsTo 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.

【 授权许可】

CC BY   
© Arias-Pulido et al.; licensee BioMed Central Ltd. 2012