Vascular endothelial growth factor expression is an independent poor prognostic factor for human epidermal growth factor receptor 2 positive gastric cancer

Background: The positive expression of human epidermal growth factor receptor 2 (HER-2) is phenotypically associated with differentiated gastric cancer (GC) and is a prognostic factor for resectable GC. The aim of this study was to explore the clinical significance of vascular endothelial growth factor (VEGF), protein kinase B, and p38 mitogen-activated protein kinase (MAPK) regarding outcome in patients with HER-2 positive GC, and to analyze the relationship between these molecules and clinicopathologic parameters.

Materials and methods: Between January 2001 and December 2012, radical-intent gastrectomy specimens from GC patients were evaluated for HER-2 expression by immunohistochemistry (IHC); and with HER-2 expression levels of 2+ were further subjected to fluorescence in situ hybridization analysis. HER-2 positivity was defined by a HER-2 3+ score on IHC or a HER-2 2+ score on IHC and HER-2 amplification by fluorescence in situ hybridization. The expression of VEGF, phosphorylated protein kinase B, and phosphorylated p38 MAPK in HER-2 positive specimens was scored using IHC.

Results: Fifty-four patients with HER-2 positive stage I-III GCs were identified. Univariate analysis of prognostic factors showed that tumor differentiation, the presence of vascular invasion, and overexpression of p-p38 MAPK, and VEGF significantly affected prognosis. Multivariate analysis identified vascular invasion (hazard ratio = 2.704; 95% confidence interval = 1.074-7.088; P < 0.033) and the overexpression of VEGF (hazard ratio = 2.760; 95% confidence interval = 1.083-6.753; P < 0.035) to be independent prognostic predictors of HER-2 positive GC.

Conclusions: VEGF overexpression and the presence of vascular invasion were independent poor prognostic factors for HER-2 positive GCs.