Tumor stromal vascular endothelial growth factor A is predictive of poor outcome in inflammatory breast cancerReport as inadecuate




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BMC Cancer

, 12:298

First Online: 19 July 2012Received: 08 November 2011Accepted: 19 July 2012DOI: 10.1186-1471-2407-12-298

Cite this article as: Arias-Pulido, H., Chaher, N., Gong, Y. et al. BMC Cancer 2012 12: 298. doi:10.1186-1471-2407-12-298

Abstract

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.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-12-298 contains supplementary material, which is available to authorized users.

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Author: Hugo Arias-Pulido - Nabila Chaher - Yun Gong - Clifford Qualls - Jake Vargas - Melanie Royce

Source: https://link.springer.com/







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