Jun-Te Hsu1, Tai-Di Chen2, Huei-Chieh Chuang2, Shih-Chiang Huang2, Puo-Hsien Le3, Tsung-Hsing Chen3, Chun-Jung Lin3, Ta-Sen Yeh4. 1. Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: hsujt2813@adm.cgmh.org.tw. 2. Department of Pathology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. 3. Department of Gastroenterology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. 4. Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Abstract
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.
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.