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

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• 作者：Jun-Te Hsu ; MD^a ; ^{hsujt2813@adm.cgmh.org.tw} ; Tai-Di Chen ; MD^b ; Huei-Chieh Chuang ; MD^b ; Shih-Chiang Huang ; MD^b ; Puo-Hsien Le ; MD^c ; Tsung-Hsing Chen ; MD^c ; Chun-Jung Lin ; MD^c ; Ta-Sen Yeh ; MD ; PhD^a
• 关键词：VEGF ; HER-2 ; Gastric cancer ; Prognostic factor ; Angiogenesis
• 刊名：Journal of Surgical Research
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：208
• 期：Complete
• 页码：40-50
• 全文大小：2094 K
• 卷排序：208

文摘

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 methodsBetween 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.ResultsFifty-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.ConclusionsVEGF overexpression and the presence of vascular invasion were independent poor prognostic factors for HER-2 positive GCs.